OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective: To investigate the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Haishu District, Ningbo City, Zhejiang Province from 2011 to 2022, so as to provide the basis for the formulation of HFMD prevention and control strategies. Methods: Data of HFMD in Haishu District from 2011 to 2022 were collected from Chinese Disease Prevention and Control Information System, and the epidemiological and etiological characteristics were analyzed using a descriptive epidemiological method. The trends in incidence of HFMD and prevalence of positive etiological tests were analyzed using annual percent change (APC). Results: A total of 33 334 cases of HFMD were reported in Haishu District from 2011 to 2022, with an average annual reported incidence of 279.16/105, showing no significant trend (APC=-5.492%, P>0.05). The average annual reported incidence of HFMD was lower after the enterovirus 71 vaccine was launched (from 2017 to 2022) than before (from 2011 to 2016; 219.69/105 vs. 343.70/105, P<0.05). The incidence of HFMD showed seasonal characteristics, with a peak from May to July. There were 19 720 male and 13 614 female cases, with a male-to-female ratio of 1.45∶1. The age of the HFMD cases ranged from 27 days to 63 years old, and the children aged 5 years and below were predominant (30 657 cases, 91.97%). A total of 1 976 specimens of HFMD cases were collected from 2011 to 2022, and 1 509 enterovirus positive specimens were detected, with a positive rate of 76.37%. The positive rates of enterovirus 71 decreased (APC=-32.599%, P<0.05), the positive rates of coxsackievirus A16 increased (APC=9.226%, P<0.05), while the positive rates of other enteroviruses showed no significant change (APC=0.808%, P>0.05). Conclusions The average annual reported incidence of HFMD in Haishu District from 2011 to 2022 decreased after the enterovirus 71 vaccine was launched, with a peak in spring and summer. Children aged 5 years and below were the high-incidence population, and coxsackievirus A16 was the main serotype.

Purpose/Significance To deeply analyze the research progress on the application of medical knowledge graph in the field of stroke,to discuss the problems of the development of stroke knowledge graph in China,and to put forward suggestions for the construc-tion of stroke knowledge graph.Method/Process By reviewing and analyzing the relevant literature,the application of medical knowledge graph in the field of stroke is sorted out and summarized.Result/Conclusion There are still many deficiencies in the development of stroke knowledge graph in China,and in the future,in-depth research can be carried out from four aspects,namely,expanding the ap-plication scope of knowledge graph,promoting the fusion of knowledge graph,developing more efficient algorithms,and upgrading to cog-nitive graph by joint artificial intelligence(AI).

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objective:To investigate the efficacy, safety and possible mechanisms of celecoxib as an adjunctive treatment for schizophrenia.Methods:90 schizophrenic inpatients at the second affiliated hospital of Xinxiang Medical College from April 2019 to October 2020 were recruited and randomly assigned to a placebo group or the celecoxib adjunctive treatment group using a random number table. In the placebo group, 46 patients (29 males, 17 females; aged 21-34, mean age 27.46±6.50 years) completed a 6-week follow-up. In the celecoxib group, 44 patients (32 males, 12 females; aged 21-39, mean age 30.52±8.69 years) completed a 6-week follow-up. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms in both groups. Changes in PANSS score at the end of the treatment were compared to evaluate the efficacy of celecoxib. Metabolic indicators such as weight, body mass index, waist circumference and plasm glucolipid, as well as cardiovascular indicators like blood pressure, electrocardiogram and routine blood tests, and adverse events were collected for the safety evaluation. Serum tumor necrosis factor-α (TNF-α), Interleukin-4 (IL-4) and interferon-γ (IFN-γ) were also tested. Pearson correlation analysis was used to explore the relationship between cytokine levels, PANSS score, PANSS reduction rate [(pre-treatment score-post-treatment score)/pre-treatment score×100%], and the safety measurements in the two groups, analyzing the role of inflammation in celecoxib adjunctive therapy.Results:The change of PANSS positive score at the end of the 6th week was significantly higher in the celecoxib adjuvant treatment group than in the placebo group (-8.00±6.12 vs -4.78±5.19, H=-0.55, P=0.009). The weight changes, body mass index, total cholesterol, and triglycerides over 6 weeks were significantly lower in the celecoxib group compared to the placebo group ( F=-7.37, -7.30, 2.56, -2.54; all P<0.05). No serious adverse events were found in celecoxib adjuvant therapy. In the placebo group, baseline TNF-α levels were positively correlated with baseline negative symptoms and PANSS reduction rate ( r=0.260 and 0.330, both P<0.05), and negatively correlated with the 6-week weight ( r=-0.311, P<0.05); baseline IL-4 levels were positively correlated with the 6-week PANSS total score and the 6-week PANSS negative score ( r=0.320 and 0.397, both P<0.05), and negatively correlated with PANSS reduction rate and 6-week blood glucose ( r=-0.316 and -0.331, both P<0.05); Six-week IFN-γ levels were negatively correlated with low-density lipoprotein levels ( r=-0.306, P<0.05). And no such correlation was found in celecoxib adjuvant group. Conclusion:Celecoxib adjunctive therapy can improve positive symptoms of schizophrenia without causing adverse reactions. Inflammatory state is related to schizophrenia symptoms, treatment efficacy and metabolic abnormalities.

Objective:To investigate the effect of patellar replacement and patellar height on the therapeutic effect of total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted on 429 patients (92 males, 337 females; aged 66.81±7.05 years; left=226, right=203) with severe knee osteoarthritis who underwent TKA in the First Affiliated Hospital of Shandong First Medical University from July 2020 to December 2021, with the body mass index of 27.60±4.22 kg/m 2, Grade-III Kellgren-Lawrence, and Insall-Salvati (IS) ratio >0.8. Afterward, the patients were divided into 4 groups according to whether patellar replacement was performed or not and the preoperative IS ratio (IS of 0.8-1.2 for normal patellar and >1.2 for high patellar): the patellar replacement+normal height patellar group (263 cases), the patellar replacement+high height patellar group (66 cases), the patellar non-replacement+normal height patellar group (68 cases), and the patellar non-replacement+high height patellar group (32 cases). Moreover, postoperative intergroup IS ratio, Knee Society Score (KSS), Hospital for Special Surgery (HSS) knee score, Oxford Knee Score (OKS), knee range of motion, complications, and satisfaction were analyzed. Results:All patients were followed up, and the time was 1.15±0.16 years (range, 1-2 years). Postoperative symptoms such as knee pain, swelling, and limitation of movement were significantly improved compared with the preoperative period. Additionally, KSS pain score, knee range of motion, HSS score and OKS score were significantly different among the four groups ( F=9.49, P<0.001; F=11.09, P<0.001; F=6.74, P<0.001; F=3.24, P=0.022), but the difference in KSS functional scores was not statistically significant ( F=1.84, P=0.140). At the same time, the KSS pain score, HSS score, OKS score, and knee range of motion (41.84±5.25, 80.43±6.99, 14.27±5.39, and 122.33°±4.93°) in the patellar replacement+normal height patella group were all better than those in the patellar non-replacement +normal height patella group (38.31±7.31, 77.00±7.81, 16.05±5.81, 120.99°±4.90°) and patella non-replaced + high height patella group (37.97±7.28, 75.62±11.02, 16.63±6.67, 116.25°±13.08°), with statistically significant differences ( P<0.05). The patella replacement+ high height patella group only had better KSS pain scores than the patella non-replaced+normal height patella group and the patella non-replaced+high height patella group (41.74±6.35, 38.31±7.31, 37.97±7.28), with statistically significant differences ( P<0.05). Moreover, Knee mobility was better in the patellar replacement+high height patella group (121.68°±2.88°) and the patellar non-replacement+normal height patella group (120.99°±4.90°) than in the patellar non-replacement+high height patella group (116.25°±13.08°), and the differences were statistically significant ( P<0.05). There were statistically significant differences in the IS ratio before surgery, 1 day after surgery and 1 year after surgery among the four groups ( P<0.05), and the IS ratio at 1 day after surgery was lower than that before surgery with statistically significant differences ( P<0.05), but there was no statistically significant difference between the IS ratio at 1 year after surgery and that before surgery ( P>0.05).Furthermore, the preoperative differences in the incidence of anterior knee pain, patellar clicking and satisfaction rates in patients with different patellar heights were not statistically significant ( P>0.05). Finally, the patellar replacement group possessed a lower incidence of anterior knee pain (normal height patella: 7.6% vs. 16.2%, χ 2=4.68, P=0.031; high height patella: 9.1% vs. 25.0%, χ 2=4.46, P=0.035) and patellar clicking (normal height patella: 9.1% vs. 17.6%, χ 2=4.05, P=0.044; high patella: 13.6% vs. 31.2%, χ 2=4.28, P=0.039); there was no significant difference in satisfaction rate among the four groups after operation ( P>0.05). Conclusion:Postoperative outcomes were better in patients with patellar replacement during TKA than in patients with no patellar replacement, and knee range of motion was better in patients with normal-height patellas than in patients with high patellas preoperatively, with no effect of TKA on patellar height.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective To investigate the treatment efficacy of lumbar spondylolisthesis patients with modic change. Methods The da-ta of 45 lumbar spondylolisthesis patients with modic change were analyzed retrospectively,which were admitted into hospital from January 2010 to December 2013 and received posterior lumbar interbody fusion ( PLIF) surgery. Those patients were tested by X-ray and Magnetic resonance imaging ( MRI) and confirmed the type of spondylolisthesis and Modic change. Based on the degree of spondylolysis and whether combined or not with Modic change,all the patients were divided into six groups:group A with Ⅱ grade spondylolisthesis;group B with Ⅲgrade spondylolisthesis;group C with Ⅱ grade spondylolisthesis with Modic typeⅠ;group D withⅡgrade spondylolisthesis with Modic typeⅡ;group E with Ⅲ grade spondylolisthesis with Modic type Ⅰ;group F with Ⅲ grade spondylolisthesis with Modic type Ⅱ. Those patients were evaluated preoperatively and postoperatively the scores according to the Visual Analogue Scale ( VAS) and Oswestry Disability Index ( ODI) systems,the obtained data were statistically analyzed and then were used to evaluated the treatment efficacy. Results The treatment efficacy of those patients were evaluated by follow-up work based on the scores of VAS and ODI systems,the results indicated that all those patients were improved in the scores of pain and ODI at different agrees. Within groups,the scores of low back and leg pain in VAS system and ODI preoperative were all significantly lower than that of postoperative (P<0. 0001). However,there were no significant differences of those scores among groups (P>0. 05). Conclusion Those spondylolisthesis patients with Modic change could obtained satisfactory clinical efficacy after posterior lumbar interbody fusion ( PLIF) surgery.

Objective To explore neurobiological mechanisms of the withdrawal-induced aversion,the changes of protein kinase A(PKA) were measured in shell of accumbens nucleus (AcbSH) of CPA model rats.Methods 1.All 36 male SD rats were divided into three groups,model group ( MN group),and control group (MS group and SN group).MN group was injected with morphine,6.5 days,10mg/kg,intraperitoneally (IP),twice per day,naloxone injection,0.3 mg/kg,ip,along with conditioned place aversion training,to develop the CPA model.The MS group was administrated equivalent volume of morphine and saline.Also the SN group was injected with equivalent volume of saline and naloxone.2.During the development of CPA,the expression of protein kinase A was assayed with immunohistochemistry in the AcbSH.Results Before the development of CPA,PKA expressions were no significant differences among the three groups in the AcbSH (F=2.306,P=0.130).However,after development of CPA,PKA expressions showed significant differences among the three groups(F =36.516,P =0.000).The average gray intensity of MN group (109.50 ± 4.661 ) was apparently higher than the MS group (126.50 ±3.697,P＜0.01),than the SN group (133.50 ±6.364,P＜0.01).Conclusions 1.Protein kinase A expression,leading to the aversion in the AcbSH probably is a key pathway contributing to the development of CPA.2.The neuroadaptation mediated by PKA may be one of important molecular underpinnings of CPA.