BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective To explore the association between different levels of fluoride exposure and dyslipidemia in elderly people, and to analyze the influencing factors and their interactions. Methods A total of 1 143 elderly people over 60 years old were randomly selected from historical high water fluorosis areas and control areas in Tianjin. Logistic regression model and classification tree model were used to analyze the influencing factors of dyslipidemia, and to analyze the interaction between high fluoride exposure and relevant influencing factors on dyslipidemia. Results The prevalence of elevated low density lipoprotein cholesterol (LDL-C) was 5.69% (65/1 143). There was a significant difference in the prevalence of high LDL-C in different fluoride-exposed areas (2 = 0.092，P = 0.762). Multivariate logistic analysis showed that high fluoride exposure (OR=2.306，95%CI：1.185-4.491) and abdominal obesity (OR=2.274，95%CI：1.299-3.978) were risk factors for high LDL-C, while type B personality (OR=0.529，95%CI：0.308-0.908) was a protective factor for high LDL-C. The results of classification tree model showed that abdominal obesity contributed the most to the prevalence of high LDL-C in the elderly, followed by high fluoride exposure and hyperglycemia. There was a significant multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia (OR=5.191,95%CI：1.609-16.745，P=0.006). Conclusion High fluoride exposure may increase the risk of high LDL-C, and there is a multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia.

Beta-thalassemia major(β-TM)is an inherited disease caused by a defect in the synthesis of globin. The disease requires long-term blood transfusion and iron chelator treatment, which can cause various secondary changes in the body and eye tissues. Compared with normal peers, β-TM patients will show changes in the eye such as steeper corneal curvature, shallower anterior chamber, increased lens thickness, shorter axial length, and reduced tear secretion. At the same time, nutritional deficiencies and the use of iron chelator drugs will increase the risk of complicated cataract and retinal degeneration, thus affecting the quality of life of β-TM patients.This article combines relevant domestic and foreign literatures to explore and review the changes in the eye of β-TM patients, with a view to providing valuable insights for clinical practice.

Objective To investigate the status and the influencing factors of thyroid volume of children aged 8-10 years in Tianjin. Methods Among the 1-2 primary schools were randomly selected from 12 districts in Tianjin. A total of 1 090 children were selected by class cluster sampling method (half male and half female, with a balanced age distribution). A questionnaire survey was conducted. Children’s height, weight and thyroid volume were measured, and their salt iodine content and urinary iodine content were detected. Results I n this study, the median urinary iodine in children was 161.35 µg/L, the mean thyroid volume was 2.56 mL, and the goiter rate was 3.58%. Univariate analysis showed that age, BSA, salt iodine content, urinary iodine content, eating habits, food taste, eating lunch at school, father's work, anxiety and depression, pressure, and different regional grouping were the influencing factors of thyroid volume (P<0.05). Multivariate linear regression showed that BSA, age, food taste, and urinary iodine content had significant independent effects on thyroid volume (P<0.05). Conclusion In Tianjin, the iodine nutrition level of children aged 8-10 years is at an appropriate level. When evaluating the thyroid volume of children, in addition to age factors, other factors such as physical development level and iodine intake should also be considered.

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P<0.01), and there was no difference in UCVA and SE between the two groups(P>0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P<0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P<0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.

OBJECTIVE To investigate the effect of myricetin(Myr) on immune function in rats with inflammatory bowel disease(IBD) by regulating the cAMP/PKA/CREB signaling pathway. METHODS IBD rat models were established and separated into control group, model group, low, medium, and high dose Myr(Myr-L, Myr-M, Myr-H, 28, 56, 112 mg·kg−1·d−1 Myr) groups, and high dose Myr+PKA inhibitor H89(Myr-H+H89 112 mg·kg−1·d−1 Myr+7 mg·kg−1·d−1 H89) group. The disease activity index(DAI) of rats was scored; immune function indicators and colon length were measured; the levels of IL-6, IL-17A, TNF-α, and cAMP in serum were determined by the kit; the pathological changes of colon tissue were observed by HE staining; the proportion of Treg cells was determined by flow cytometry; immunohistochemistry was used to detect the expression of MPO in colon tissue; Western blotting was used to determine cAMP/PKA/CREB signaling pathway related proteins. RESULTS Compared with the control group, the colon tissue cells in the model group were disorderly arranged, with a large number of inflammatory cell infiltration, severe ulceration, a large number of cell necrosis, mucosal edema, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). Compared with the model group, the arrangement of colon tissue cells in the Myr-L, Myr-M, and Myr-H groups was relatively neat; mucosal edema inflammatory cell infiltration, cell necrosis and ulcer phenomenon were reduced; the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were gradually reduced(P<0.05); the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were gradually increased(P<0.05). Compared with the Myr-H group, the pathological changes in the colon tissue of the Myr-H+H89 group worsened, the DAI score, IL-6, TNF-α, and IL-17A levels, spleen coefficient, thymus coefficient, and MPO optical density values were obviously increased(P<0.05), the colon length, Treg cell ratio, cAMP concentration, p-PKA/PKA, and p-CREB/CREB levels were obviously reduced(P<0.05). CONCLUSION Myr may inhibit inflammation levels, regulate immune function, and exert protective effects on IBD rats by activating the cAMP/PKA/CREB signaling pathway.

Dissipative structure refers to a self-organized and orderly structure that exists far from equilibrium.The human body,considered a classical example,generates negative entropy through the exchange of matter,energy,and information with the environment to counteract the increase in entropy.In this paper,we organized theories and related research on dissipative structure and entropy,discussing their significance in regulating various aspects such as the human body,cancer,aging,and more.By selecting the special population of pregnant women,focusing on the information dimension,developing the corresponding information exchange scale(Cronbach's α>0.9),and proposing the information exchange index,we preliminarily explored the influence of the dissipative structure's information dimension on pregnancy health.The results showed a negative correlation between the information exchange index and anxiety scores during pregnancy(r =-0.35,P<0.001),with an OR value of 0.26(95%CI:0.08～0.80),preliminarily confirming the feasibility of conducting empirical research based on dissipative structure theory.If further relevant empirical studies are conducted,it is expected that new disease prevention strategies will be developed and new theories and methods will be provided for the field of public health.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.