OBJECTIVES: Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of WNT10A gene knockdown in PTC cell proliferation, invasion, and metastasis. METHODS: The expression of WNT10A in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure WNT10A mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by WNT10A were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway. RESULTS: WNT10A mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both P<0.01). The real-time RT-PCR result showed that WNT10A mRNA expression in PTC tissues was high than that in adjacent tissues (P<0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (P<0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. WNT10A knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all P<0.01). WNT10A silencing also reduced migration and invasion abilities in both cell lines. In vivo, WNT10A knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that WNT10A knockdown downregulated the expression of key genes (STAT3, MAPK8, TNFRSF21, and AKT2) in this pathway. CONCLUSIONS WNT10A is highly expressed in PTC and is associated with tumor proliferation, invasion, and metastasis. Its tumor-promoting effects may be mediated through suppression of the Tec kinase signaling pathway.
Humans ; Cell Proliferation ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/metabolism* ; Animals ; Wnt Proteins/metabolism* ; Neoplasm Invasiveness ; Mice ; Cell Line, Tumor ; Female ; Male ; Mice, Nude ; Apoptosis ; Lymphatic Metastasis ; Middle Aged ; Cell Movement ; Adult

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To describe the epidemiological characteristics and trends of leukemia incidence in Qidong between 1972 and 2021, and provide guidelines for prevention and control measures and strategies.Methods:The cancer registry data was collected and analyzed on leukemia incidence during 1972—2021 in Qidong by sex, age and time. Crude incidence rate (CR), China age-standardized rate (ASRC), world age-standardized rate (ASRW), and average annual change percentage (AAPC) was calculated by Joinpoint software. Age-period-cohort (APC) model was used to analyze the influence of age, period and birth cohort on the changes in the incidence trend of leukemia patients.Results:From 1972 to 2021, there were 2 948 patients with leukemia in Qidong, accounting for 2.00% of all cancer new cases, CR of leukemia was 5.26/10 5, ASRC was 4.34/10 5, ASRW was 4.35/10 5. The truncated incidence of 35—64 years old was 5.29/10 5, the cumulative incidence rate between the ages of 0 and 74 years old was 0.40%, the cumulative risk was 0.40%. There were 1 608 male patients, the CR, ASRC, and the ASRW were 5.81/10 5, 4.88/10 5 and 4.85/10 5. The number of female patients were 1 340, and the CR, ASRC, and the ASRW were 4.71/10 5, 3.86/10 5 and 3.91/10 5, respectively. Temporal trends indicated significant upward trends in ASRC among both gender, males and females with AAPC values of 1.41% ( P＜0.001), 1.15% ( P＜0.001), and 1.73% ( P＜0.001), respectively. The results of the APC model showed that the average net drift value of leukemia incidence in all age groups was 1.57% (95% CI, 1.24%-1.89%), and the highest value of local drift was 3.20% (95% CI, 1.63%-4.78%) in the 80~ years old group. The incidence of leukemia increased with age. With the passage of time, the risk of leukemia incidence increased gradually compared with the rate ratio of leukemia incidence (risk ratio [ RR], 1.00) in 1992—1996, the RR of leukemia incidence increased from 0.70 during 1972—1976 to 1.57 during 2017—2021. The later the cohort was born, the greater the risk of leukemia incidence compared with the relative risk of leukemia incidence ( RR, 1.00) in 1952—1956 cohort, the RR of leukemia incidence increased from 0.24 in the 1892—1896 cohort to 2.73 in the 2017—2021 cohort. Conclusions:The incidence of the leukemia has presented a rising trend in the past fifty years. Leukemia incidence increased with age, and the period and cohort effects on the risk of incidence increase. Further research is needed to investigate the risk factors related to leukemia.

Promoting the transformation and development of public hospitals into clinical research-oriented hospitals is the necessary way for China to deepen the reform of medicine and health system. In August 2019, Henan Cancer Hospital deeply combined the key elements of clinical research management with the concept of multidisciplinary collaborative governance, created an offline operating end of collaborative governance (including the front collaborative recruitment system, the middle collaborative quality management system, and the terminal collaborative transformation system), built a supporting internet plus intelligent auxiliary end (including the intelligent recruitment manager, the intelligent quality manager and the intelligent transformation manager), and built a clinical research intelligent management mode covering the trinity of subject recruitment, clinical research quality control, and innovation achievements transformation. The hospital focused on management elements such as " focusing on quality, improving efficiency, and increasing motivation" , and drove the front, middle, and terminal ends of the model to work together, to ensure the quality and efficiency of clinical research and achieve a comprehensive improvement in the hospital′s clinical research level. As of December 2023, the hospital had undertaken over 2 000 clinical research projects of various types, with a cumulative amount of clinical research conversion contracts exceeding 53 million yuan. This practice had achieved good results and could provided references for other tertiary public hospitals to promote high-quality development of clinical research.

Objective To investigate the efficacy of rituximab combined with immunosuppressive pulse therapy for thyroid-associated ophthalmopathy(TAO)and analyze its influence on clinical activity score(CAS)and prognosis.Meth-ods A total of 136 patients(272 eyes)with TAO who were admitted to Huanggang Central Hospital from March 2020 to October 2022 were selected and divided into an observation group(68 patients)and a control group(68 patients)using a random number table method.Patients in the control group were given immunosuppressive pulse therapy,while patients in the observation group were given rituximab plus immunosuppressive pulse therapy.Both groups were treated for 4 courses(7 days per course).The clinical efficacy,eye signs,CAS score,thyroid conditions[thyrotropin receptor antibody(TRAb),thyroid peroxidase antibody(TPOAb),thyroid volume],T lymphocyte subsets,and adverse reactions were compared between the two groups.After a follow-up period of six months,the prognosis of patients in the two groups was compared.Results After 4 courses of treatment,the total effective rate of patients in the observation group was 94.12％(64/68),which was higher than that in the control group(82.35％,56/68)(P＜0.05).After 2 and 4 courses of treat-ment,the degree of exophthalmos,intraocular pressure,average palpebral fissure width,retrobulbar soft tissue volume,distance from the bulbus oculi,CAS score,TPOAb,TRAb,and thyroid volume of patients in the observation group were smaller than those in the control group,and all decreased compared to before treatment(all P＜0.05);the thickness of the tear film lipid layer was greater than that in the control group,and both increased compared to before treatment(all P＜0.05).There were no significant differences in the said indicators between the two groups before treatment(all P＞0.05).The CD3+,CD4+,and CD8+T lymphocyte levels of patients showed no significant difference between the two groups before treatment(all P＞0.05).After 2 and 4 courses of treatment,the levels of CD3+and CD4+T lymphocyte in both groups were higher than those before treatment.Except that the CD4+T lymphocyte level in the observation group was lower than that in the control group after 2 courses of treatment,the levels of CD3+and CD4+T lymphocyte in the obser-vation group were higher than those in the control group at other time points(all P＜0.05).After 2 and 4 courses of treat-ment,the level of CD8+T lymphocyte in both groups decreased compared to before treatment,and it was lower in the ob-servation group than the control group(all P＜0.05).There was no significant difference in the incidence of adverse reac-tions such as low fever,nausea,and hypokalemia between the two groups(all P＜0.05).After the 6-month follow-up,the improvement rate of patients in the observation group was 95.59％(65/68),which was higher than that in the control group(79.41％,54/68)(P＜0.05).Conclusion Rituximab combined with immunosuppressive pulse therapy is effec-tive for TAO.It can alleviate eye signs and thyroid conditions,reduce clinical activity,and promote prognosis.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To explore the status of microsatellite instability (MSI) and its relationship with clinicopathological characteristics of patients with endometrial carcinoma.Methods:The clinical data of 365 patients with endometrial carcinoma who received surgery in Shanxi Province Cancer Hospital between January 2020 and December 2021 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of 4 DNA mismatch repair (MMR) proteins (MLH1, MSH2, MHS6, and PMS2), estrogen receptor (ER), progesterone receptor (PR), and p53 mutant protein in postoperative cancer tissue samples from 365 patients with endometrial carcinoma. All patients were divided into MSI group (1 or more non-expression of MMR protein) and microsatellite stability (MSS) group (4 proteins were all expressed), and the clinicopathological characteristics of patients in both groups were compared. φ efficient was used to analyze the correlation of MSI with ER, PR, p53 mutant protein expressions. Results:There were 72 cases (19.7%) in MSI group and 293 cases (80.3%) in MSS group; and the age of all patients was (53±19) years (21-83 years). There were statistically significant differences in the proportion of MSI patients in endometrial carcinoma patients with different age [>50 years vs. ≤50 years: 22.1% (61/276) vs. 12.4% (11/89)], tumor diameter [≤2 cm vs. > 2 cm: 25.9% (30/116) vs. 16.8% (42/249)], International Federation of Gynecology and Obstetrics (FIGO) staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 31.1% (14/45) vs. 18.1% (58/320)], histological type [type Ⅰ vs. type Ⅱ: 21.7% (71/327) vs. 2.6% (1/38)] (all P < 0.05). There were no statistically significant differences in the proportion of MSI patients with different depth of invasion, degree of differentiation, lymph node metastasis, vascular involvement, and lesion location (all P > 0.05). Among 327 cases of type Ⅰendometrial carcinoma, 1 case was mucinous adenocarcinoma (MSS status), and the other 326 cases were endometrioid adenocarcinoma. Of the 72 patients with MSI, 71 cases were endometrioid carcinoma and the other was 1 of 3 mixed carcinomas in type Ⅱ endometrial carcinoma. There was a negative correlation between MSI and mutant p53 ( φ coefficient was -0.11, P = 0.031), and φ coefficient of the correlation of MSI with ER and PR was -0.03 and -0.06, while there were no statistically significant differences ( P value was 0.578 and 0.255, respectively). Conclusions:Endometrioid adenocarcinoma is the main type of endometrial cancer patients with MSI. MSI in endometrial cancer is correlated with age, FIGO staging, tumor diameter and histological type of patients, while negatively correlated with mutant p53.