BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

An analysis was conducted on the clinical manifestations, auxiliary examinations, diagnosis and treatment process, treatment, and prognosis of a child with neurobrucellosis. 408 relevant literature on neurobrucellosis from January 2012 to December 2022 were searched through Chinese and English databases such as CNKI, Wanfang Data, and Biomedical Literature Database (PubMed). Literature was screened based on inclusion and exclusion criteria, A total of 14 children with neurobrucellosis were selected for analysis, with an average age of onset of 10 years old. Among the patients, there were 3 cases of middle cranial nerve injury, 2 cases of ataxia, 1 case of myelitis, 2 cases of mental symptoms, 1 case of optic disc edema, 1 case of sagittal sinus thrombosis, and the rest were manifested as meningitis and encephalitis. The imaging results suggested that there was often no specific area of invasion, with magnetic resonance imaging (MRI) commonly involving the cortex, central half oval, and basal ganglia. Extensive white matter changes were also frequently observed, which is consistent with the findings of this case report. Neurobrucellosis has diverse clinical manifestations and lacks specificity. It is mainly diagnosed based on comprehensive analysis of neuropsychiatric symptoms, cerebrospinal fluid and serological results, imaging characteristics, etc. Early diagnosis and treatment are of great significance in preventing complications of neurobrucellosis.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Objective:To investigate the association of total sleep time (TST) and oxygen desaturation index (ODI) with hypertension in patients with obstructive sleep apnea/hypopnea syndrome (OSA).Methods:A total of 440 OSA patients admitted to Yixing Hospital from January 2017 to December 2022 were consecutively enrolled, including 236 patients with hypertension (OSA+hypertension group) and 204 patients without hypertension (OSA group). The clinical data and polysomnograpic parameters were collected. Univariate and multivariate logistic regression was used to analyze the related factors of OSA complicated with hypertension. The multiplicative interaction between TST and ODI on OSA with hypertension was analyzed. A two-factor cross-over analysis of TST and ODI was performed and the additive interaction model was used to analyze the additive interaction between TST and ODI on OSA with hypertension.Results:Univariate logistic regression showed that male sex, smoking, diabetes, coronary heart disease, TST <7 h, age, body mass index, neck circumference, waist circumference, Epworth Sleepiness Scale (ESS) score, TST, AHI, ODI>16 times/h, triglyceride, high density lipoprotein cholesterol and fasting blood glucose were positively correlated with hypertension in OSA patients (all P<0.05). Multivariate logistic regression analysis showed that smoking ( OR=4.327, 95% CI: 2.499-2.499, P<0.001), TST<7 h ( OR=1.748, 95% CI: 1.079-2.832, P=0.023) and ODI>16 times/h ( OR=3.482, 95% CI: 2.016-6.014, P<0.001) were independently associated with hypertension in OSA patients. After introducing a multiplicative term and adjusting for confounding factors, there was a positive multiplication interaction between TST <7 h and ODI>16 times/h ( OR=2.958, 95% CI: 1.079-8.113, P<0.050). Multivariate logistic regression analysis showed that the risk of hypertension in OSA patients with TST<7 h and ODI>16 times/h was 7.196 times (95% CI: 3.421-15.137) higher than that in patients with TST≥7 h and ODI≤16 times/h. The additive interaction model showed a synergistic effect between TST<7 h and ODI>16 times/h, with S value of 4.302 (95% CI: 1.566-11.815), RERI value of 4.756 (95% CI: 0.642-8.869) and API value of 66.10% (95% CI: 43.10%-89.10%). Conclusion:Shortened sleep duration and increased ODI are independent risk factors for hypertension in OSA patients, and when they coexist, the risk of hypertension in OSA patients is further increased.

Objective:To provide scientific basis for prevention and control measures of island regions through analyzing the characteristics of malignant tumor incidence and mortality in eastern island areas of China and comparing the data with the national cancer mortality data in the same period. Methods:Using the incidence and mortality data of malignant tumor in Daishan county,Zhoushan collected by the Daishan Center for Disease Control and Prevention(CDC)from 2014 to 2019,which was stratified by gender,the crude incidence rates(CIR)and crude mortality rates(CMR)were calculated,and the top 10 malignant tumors with the highest incidence or mortality rates were then ranked.The Segi's world standard population was used to calculate the age-standardized incidence(ASIR)and age-standardized mortality rate(ASMR).The local data were compared with the national cancer mortality data from 2014 to 2019,and Chi-square test was used to analyze the differences between these two sets of data using the SPSS software.The difference was considered statistically significant when P<0.05. Results:There was a total of 7 305 incidence cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CIR was 662.39/105 and the ASIR was 306.81/105.Notably,the CIR was the highest in the age group of 75-79 years old.The top 5 malignant tumors with the highest incidence rates were lung cancer(27.15％),gastric cancer(12.76％),liver cancer(10.95％),colorectal cancer(6.92％)and breast cancer(5.42％),whose ASIR were 75.09/105,32.06/105,31.01/105,17.81/105 and 18.36/105,respectively.There was a total of 3 412 mortality cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CMR was 309.39/105 and the ASMR was 122.73/105.Notably,the CMR was the highest in the age group of 80-85 years old.The top 5 malignant tumors with the highest mortality rates were lung cancer(24.94％),liver cancer(18.64％),gastric cancer(17.00％),colorectal cancer(7.56％)and esophageal cancer(5.72％),whose ASMR were 29.65/105,24.97/105,19.01/105,8.75/105 and 6.60/105,respectively.The total ASMR of malignant tumors in Daishan county,Zhoushan was higher than national total ASMR from 2014 to 2019(100.34/105)(P<0.001).Specifically,the ASMR of gastric cancer,lung cancer and colorectal cancer in Daishan county were significantly higher than national levels(gastric cancer:12.46/105;liver cancer:16.45/105;colorectal cancer:6.63/105)(P<0.01),whereas no significant difference in the ASMR of lung cancer and esophageal cancer between Daishan county and the whole nation(lung cancer:28.06/105;esophageal cancer:7.61/105)was observed. Conclusion:Lung cancer,gastric cancer,liver cancer and colorectal cancer were malignant tumors with higher incidence and mortality rates in Daishan county,Zhoushan from 2014 to 2019.Particularly,the ASMR of gastric cancer,liver cancer and colorectal cancer were significantly higher than the national levels,and these malignant tumors should be considered as the major focus of cancer prevention and control.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Objective To explore the humidification effects between the humidifiers Venturi high-flow oxygen therapy(HVHF)and the high-flow humidified oxygen therapy in the treatment of patients with tracheotomy after the withdrawal of ventilator,and analyse the humidification performance and effect of airway humidification on the two oxygen therapies hence to provide an objective basis for selection of a humidified oxygen therapy.Methods A total of 146 ICU patients who had tracheotomy and completely withdrawal of ventilator in a general hospital in Shenzhen from July 2020 to December 2021 were randomly divided into trial group(n=73)and control group(n=73).With identical speed of airflow,patients in the trial groups were treated with HVHF and the patients of control group were offered with high-flow humidified oxygen therapy via AIRVOTM2.Data of the two groups were compared at the time points of days 0,2,7 and 14 in terms of absolute humidity(AH),relative humidity(RH),temperature(T)),sputum viscosity,arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),oxygenation index(PaO2/FIO2)and the incidence of pulmonary infection.Results In the study,total of 61 patients in the control group and 72 patients in the trial group completed the high-flow humidified oxygen therapies,due to tubing detachments in 12 and 1 patients in the two groups,respectively.Repeated-Measures ANOVA analysis showed that,in both groups,there was a time effect(P<0.05)between the absolute humidity,relative humidity,temperature of the gas,PaO2,PaCO2,and PaO2/FiO2 at different time points.PaO2 and PaO2/FiO2 in both groups showed interactions at different time points(P<0.05).PaO2 and PaO2/FiO2 in the trial group were better than those in the control group at the time points of days 2,7 and 14(P<0.05).On days 2,7 and 14,the viscosity of sputum in the intervention group was better than that in the control group,and the incidence of pulmonary infection in the trial group was significantly lower than that in the control group(P<0.05).Conclusions HVHF and AIRVOTM2 both exhibit no obvious difference in gas humidification via high-flow humidification oxygen therapy in the patients with tracheotomy after withdrawal of ventilator.However,HVHF is superior to AIRVOTM2 in terms of improving airway humidification and oxygenation as well as reducing lung infection.Therefore,it is suggested that an HVHF is preferable for high-flow humidified oxygen therapy in treating the patients with tracheotomy after the withdrawal of ventilator.

Objective:To establish a modified controlled abciximab and device investigation to lower late angioplasty complication (CADILLAC) score, and to compare the predictive value of modified CADILLAC score, the global registry of acute coronary event (GRACE) score and the thrombolysis in myocardial infarction (TIMI) score in predicting the risk of short-term death after percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction (STEMI).Methods:A retrospective study was conducted. The clinical data of 169 STEMI patients under going PCI admitted to the department of cardiology of Guizhou Provincial People's Hospital from September 2019 to December 2020 through emergency chest pain fast track were enrolled. A multivariate Logistic regression analysis was used to screen the factors closely related to the mortality risk within 30 days of STEMI, and a modified CADILLAC scoring system was established by referring to CADILLAC scoring settings. The score of modified CADILLAC, GRACE and TIMI scores of patients were calculated after admission, and the number of deaths due to cardiovascular disease (CVD) within 30 days after onset was recorded. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of three scoring systems on the risk of death within 30 days after PCI in patients with STEMI.Results:In 169 STEMI patients, 16 patients died of CVD within 30 days after PCI, and the actual case mortality was 9.47%. Multivariate Logistic regression analysis showed that age > 75 years old, cardiac function Killip ≥ Grade Ⅲ, ventricular arrhythmia, ST segment elevation ≥ 0.2 mV, cardiac troponin I (cTnI) increase, systolic blood pressure (SBP) < 90 mmHg (1 mmHg ≈ 0.133 kPa) were all independent predictors of death after PCI in STEMI patients. The improved CADILLAC scoring system was constructed based on the above predictive factors combined with left ventricular ejection fraction (LVEF) less than 0.40. The GRACE, TIMI and modified CADILLAC scores of dead patients were significantly higher than those of survival patients (GRACE score: 197.60±31.83 vs. 149.81±36.72, TIMI score: 11.21±2.13 vs. 7.27±1.97, modified CADILLAC score: 12.60±2.52 vs. 6.96±2.17, all P < 0.05). The higher the risk stratification of the three scores, the higher the mortality of patients with CVD within 30 days after PCI [the mortality of patients with low, medium and high risk in GRACE score were 2.41% (2/83), 9.61% (5/52) and 26.47% (9/34); the mortality of patients with low, medium and high risk in TIMI score were 3.12% (3/96), 12.82% (5/39) and 23.53% (8/34); and the mortality of patients with low, medium and high risk in modified CADILLAC score were 3.19% (3/94), 7.69% (4/52) and 39.13% (9/23), respectively, all P < 0.01]. The area under the ROC curve (AUC) of the GRACE, TIMI and the modified CADILLAC scores predicting the risk of death 30 days after PCI in STEMI patients were 0.855 [95% confidence interval (95% CI) was 0.702-0.923], 0.725 (95% CI was 0.666-0.812) and 0.882 (95% CI was 0.732-0.936), respectively, all P = 0.000; the sensitivity of its prediction accuracy were 81.59%, 78.65% and 89.26%, and the specificity were 78.62%, 57.12% and 75.54%, respectively. Conclusions:The GRACE and the modified CADILLAC scores have predictive value for the short-term mortality risk of STEMI patients after PCI, and the modified CADILLAC score is more accurate. But the TIMI score has a poor predictive effect on the short-term mortality risk of STEMI patients after PCI.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

ObjectiveTo compare the annual and age trends of the age-standard incidence rate （ASIR） and the age-standard mortality rate （ASMR） of lung cancer in countries with different human development index （HDI） from 1990 to 2019. MethodsThe data were collected from the global burden of disease study and GLOBOCAN 2020. The average annual percentage change （AAPC） and age trends of ASIR and ASMR in lung cancer were analyzed by the Joinpoint regression model， and the comparison between the four groups was analyzed by Kruskale-Wallis analysis. ResultsIn 2020， the incidence and mortality of lung cancer gradually increased with age and HDI grade. From 1990 to 2019， the global ASIR and ASMR of lung cancer decreased， and the ASIR of lung cancer among male decreased， while the ASIR of lung cancer among female increased. The results showed that ASIR of lung cancer in female residents in countries with very high HDI increased significantly from 1996 to 2011， resulting in an overall upward trend in female ASIR， while the other groups showed a downward trend. It was found that ASIR and ASMR of lung cancer in China and India were on the rise， while ASIR and ASMR of lung cancer in Russia and the United States were on the decline. ConclusionAlthough very high/high HDI countries face a higher burden of lung cancer occurrence and death， the accumulation of lung cancer burden is completed in the transitioning period. Therefore， lung cancer prevention measures in countries in transition are critical for global lung cancer control.