BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Objective:To observe therapeutic effect of catalpol on Sj?gren's syndrome(SS)model mice and explore further mechanism through vitro experiments.Methods:Eight-week-old NOD mice were given catalpol 100 mg/kg by gavage for 8 weeks.Serum levels of IFN-γ and IL-17 were measured.Pathological of salivary glands were observed.lnc-NONHSAT071210 shRNA trans-fected salivary gland epithelial cell lines were treated with 50 μmol/L catalpol,and expression of lnc-NONHSAT071210 was detected.Cells were intervented by 10 ng/ml IFN-γ,lnc-NONHSAT071210 shRNA and catalpol treatment for 72 h,cell proliferation and expressions of IL-17 and IFN-γ were detected.Results:Compared with control group,expressions of IFN-γ and IL-17 were decreased(P<0.05),pathology of salivary gland showed that infiltration of lymphocytes was reduced and destruction of gland structure was significantly reduced in catalpol group.Compared with IFN-γ intervention group,catalpol treatment significantly increased prolifera-tion of salivary gland epithelial cells,and decreased expressions of IFN-γ and IL-17(P<0.05).After catalpol treatment,expression of lnc-NONHSAT071210 was decreased(P<0.05).Moreover,IFN-γ and IL-17 expressions were decreased by catalpol and lnc-NONH-SAT071210 shRNA co-treatment(P<0.01).Conclusion:Catalpol can inhibit expressions of inflammatory cytokines in serum and infiltration of lymphocyte in salivary gland of SS model mice,and inhibit salivary gland ductal fine epithelial inflammatory response and progression of SS by regulating lnc-NONHSAT071210.

Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.

Objective:To analyze the iodine nutrition status and its related factors among adults aged 18 years and above in Zhejiang Province in 2022.Methods:A multistage stratified sampling method was used to select 4 320 adults aged 18 years and above from 16 on-site survey sites in Zhejiang Province for the study. A questionnaire was used to investigate the general demographic information and personal dietary characteristics of the study participants. Household edible salt and urine samples were collected to detect salt iodine content and urinary iodine level by using direct titration and cerium arsenate-catalyzed spectrophotometry, respectively, to evaluate the iodine nutritional status according to the standard. The multiple-ordered logistic regression model was used to analyze the factors influencing the urinary iodine concentration.Results:The age of the 4 320 study participants was (51.19±15.33) years, with males accounting for 44.44% (1 920). About 40.16% of adults (1 735) were from coastal areas and 56.37% (2 435) from urban areas. The salt iodine content, M ( Q1, Q3), of the 4 320 household edible salt samples was 21.10 (0.00, 24.16) mg/kg, including 1 662 non-iodized salt samples, 182 unqualified iodized salt samples and 2 476 qualified iodized salt samples. The rate of iodized salt coverage was 61.53%, and the rate of qualified iodized salt consumption was 57.31%. There was a statistically significant difference in the proportion of qualified iodized salt in adult households among different regions ( P<0.001), with the proportion of non-iodized salt gradually decreasing from coastal to inland areas ( χ 2trend=618.458, P<0.001). The urinary iodine concentration M ( Q1, Q3) was 137.60 (86.85, 210.60) μg/L in 4 320 adult urine samples, with the urinary iodine levels of<100, 100-199, 200-299, and≥300 μg/L accounting for 31.64% (1 367), 40.56% (1 752), 17.66% (763), and 10.14% (438), respectively. There was a nonlinear positive correlation between household salt iodine content and urinary iodine level in adults aged 18 years and above by using the χ 2 test for trend ( χ 2regression=231.10, P<0.001 and χ 2skew=28.81, P<0.001). Urinary iodine concentrations were higher in men than in women ( P=0.029) and higher in adults in rural areas than in urban areas ( P<0.001). There were statistically significant differences in the distribution of iodine nutritional status among adults of different ages, regions, and urban and rural areas (all P<0.001). The proportion of those with urinary iodine levels<100 μg/L gradually increased with age ( χ 2trend=37.493, P<0.001), and gradually decreased from coastal areas to inland areas ( χ 2trend=71.381, P<0.001). The results of the multiple-ordered logistic regression model analysis showed that compared with adults aged 18 to 44 years and male adults, those aged 45 to 59 years and female adults had lower urinary iodine levels, with OR (95% CI) of 0.75 (0.68-0.83) and 0.85 (0.76-0.95), respectively. Compared with adults in coastal and urban adults, those in sub-coastal, inland and rural adults had higher levels of urinary iodine, with OR (95% CI) of 1.89 (1.63-2.19), 2.02 (1.72-2.37) and 1.46 (1.28-1.66), respectively. Conclusion:The overall iodine nutrition level of adults aged 18 years and above in Zhejiang Province in 2022 is generally appropriate. However, there is a potential risk of iodine deficiency among adults in coastal areas.

Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective:To investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.

Objective:To explore the clinical characteristics, treatment, and prognosis of patients with spondyloarthritis (SpA) and clinically insignificant monoclonal garmmopathy of undetermined significance (MGUS).Methods:A retrospective study was performed to analyze the clinical characteristics of patients simultaneously diagnosed with both SpA and MGUS at the First Affiliated Hospital to Zhengzhou University between January 2020 and December 2024, supplemented by a literature review.Results:Among the 5 patients (2 males, 3 females; age range 33~65 years), 4 presented with peripheral arthritis and 2 with extra-articular manifestations. All patients demonstrated elevated globulin and IgG levels, with 4 being HLA-B27 positive. M-protein typing revealed IgG/κ in 3 cases and IgA/λ in 2. All five patients underwent both X-ray and MRI examinations, with sacroiliitis being detected in 4 cases. Three patients with long disease duration showed poor response to conventional therapy (NSAIDs/DMARDs). Targeted therapies yielded variable outcomes: one patient achieved normalized globulin/IgG levels with etanercept (3-year follow-up without MGUS progression); another showed marked clinical improvement and significant globulin/IgG reduction with JAK inhibitor (tofacitinib, treated for 7 years); while a third demonstrated no symptom relief then switching from TNF-α inhibitor to IL-17 inhibitor.Conclusion:Persistent hyperglobulinemia in SpA patients warrants MGUS screening. Those with SpA-MGUS may require targeted therapies, where JAK inhibitors and monoclonal TNF-α inhibitors appear to be the preferred options, though long-term monitoring for MGUS progression remains essential.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.