Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

Objective Analyze the surveillance results of foodborne illness from a level A tertiary general hospital in Shandong Province from 2019 to 2021,to provide a realistic basis for the continuous development and improvement of foodborne disease surveillance.Methods The data were collected from a level A tertiary general hospital in Shandong Province from 2019 to 2021 in the food safety risk assessment business application platform of national health insurance information project of National Health Security Disease Control Information System,and stool/anal swab samples were collected as required for pathogen detec-tion.Results From 2019 to 2021,a total of 2 323 cases of foodborne diseases were reported and 682 samples were collected,with a sampling rate of 29.36％,and 134 positive cases were detected,with a detection rate of 19.65％.The difference between the detection rates of different years was statistically significant(P＜0.05).The detection rate of norovirus was the highest(9.53％),followed by Vibrio parahaemolyticus(8.94％)and Salmonella(1.91％).The difference between the detection rates of different pathogens was statistically significant(P＜0.05).The sex ratio of 2 323 cases was 1:1.28.Among the different age distributions,20-29 years old accounted for the highest proportion(29.19％),followed by 30-39 years old(27.21％)and＜20 years old(11.71％).The highest number of cases was reported from June to September,the peak was reached from July to Au-gust,and the number of cases was gradually reduced in October and later.Among different occupational groups,housework and unemployed people accounted for the highest proportion(30.18％),followed by farmers(15.93％),students(13.65％)and commercial service workers(11.80％).The main symptoms of the digestive system were diarrhea in 2 093 cases(90.10％),abdominal pain in 1 741 cases(74.95％),nausea in 1 575 cases(67.8％)and vomiting in 1 401 cases(60.31％).The main diarrhea was watery stool in 1 954 cases(84.12％).The main systemic symptoms were fatigue in 454 cases(19.54％)and dehydration in 212 cases(9.13％).The main clinical diagnosis was acute gastroenteritis in 1 980 cases(85.23％)and infec-tious diarrhea in 199 cases(8.57％).The suspected exposed foods were mainly aquatic animals and their products(25.10％)and meat and meat products(19.37％).The main eating places of suspected exposed foods were families(57.34％),followed by restaurants(21.91％),other places(5.94％)and street food stalls(5.21％).Conclusion From 2019 to 2021,the pathogens of foodborne diseases detected were mainly norovirus and Vibrio parahaemolyticus,mainly in the age group of 20 to 39 years old,and the occupation distribution was mainly household and unemployed people,farmers,students and commercial serv-ice personnel,with digestive system symptoms such as nausea,vomiting,abdominal pain and diarrhea.The suspected exposed foods are mainly aquatic animals and their products and meat and meat products,and the main eating places are families,restau-rants and street food stalls.The surveillance and reporting of foodborne diseases should continue to be strengthened in the future.

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/β-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

Glioma is a tumor with a high incidence of intracranial tumor. Because of its high degree of malignancy, strong invasiveness and high mortality, the current conventional treatment cannot achieve the desired therapeutic effect, which greatly affects the quality of life of patients. As a protein with the functions of anti-proliferation, anti-angiogenesis and anti-invasion, interferon is widely used in the treatment of all kinds of tumors in clinic. Many studies have shown that interferon plays an important role in the occurrence and development of gliomas. To explore the mechanism of interferon and its related signal pathway in the process of glioma invasion, and to study the new treatment of glioma is very necessary in clinical treatment.

Intracranial aneurysm is a common cerebrovascular disease. Its rupture causes subarachnoid hemorrhage with high mortality and disability. At present, the main treatment methods of intracranial aneurysms include craniotomy clipping and intravascular embolization. With the invention of flow diverters and wide application in clinic, it has gradually become another mainstream treatment method of intracranial aneurysms. This article reviews the effectiveness, safety and cost-effectiveness of flow diverters in the treatment of intracranial aneurysms.

Objective: To investigate the efficacy and safety of Rivaroxaban for elderly patients with thrombotic diseases. Methods: This was a retrospective study.A total of 301 elderly patients taking Rivaroxaban from October 2012 to November 2017 at the Second Medical Center of the Chinese PLA General Hospital were consecutively selected.The ages ranged from 60 to 102 years, with an average age of(86.5±8.4)years.Anticoagulation regimens were developed based on comprehensive evaluation of indications, creatinine clearance, ischemia and bleeding risk.Patients were divided into a Rivaroxaban 2.5-5.0 mg/d group(n=72), a 10.0 mg/d group(n=205), and a 15.0-20.0 mg/d group(n=24). Hepatic function, renal function, and coagulation indexes were measured before and after the administration of Rivaroxaban.Fatal bleeding, cardiovascular deaths, all-cause deaths, non-fatal bleeding and thromboembolic events were recorded during the follow-up period. Results: The average dose of Rivaroxaban was(9.3±3.0)mg/d, and the minimum dose was 2.5 mg/d.The average follow-up time was(14.9± 13.9)months and the longest follow-up time was 48 months.One patient had intracranial bleeding.Twenty patients(6.6%)died with a cumulative incidence of 25.2%, three(1.0%)died of cardiac events, and 55.0% died of pneumonia and multiple organ failure.Forty patients(13.3%)had non-fatal hemorrhagic events with a cumulative incidence of 42.4%.Seven patients(2.3%)had thromboembolic events with a cumulative incidence of 16.0%, including 2 cases of non-fatal myocardial infarction, 3 cases of cerebral infarction and 2 cases of deep vein thrombosis.After treatment, levels of prothrombin time and fibrinogen significantly increased while levels of D-dimer significantly deceased(P<0.05). Conclusions Compared with previous reports, low-dose Rivaroxaban is safe and effective for elderly patients with thrombotic diseases.However, the risk of bleeding and ischemia should be comprehensively evaluated, and appropriate doses of Rivaroxaban should be selected individually.

This paper aimed at discussing the characteristics of blood glucose changes of type 2 diabetes according to the flow rule of Qi and Blood as well as the Hurst index of dynamic blood glucose collected by CGMS. A total of 156 T2DM patients were selected from the Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. After continuous monitoring of dynamic blood glucose for 3 consecutive days (72 hours) with CGMS, the first complete 24 hour dynamic glucose, which start at 3 to 5 am(corresponding to Lung) and end at 1 to 3 am next morning(corresponding to Liver), are used for calculating each two-hours?? Hurst index. The measurement data was set at each two-hours, and multiple groups of related sample tests (Friedman) non- parametric test methods were used for comparison between groups. The statistical significance level was set to P ＜ 0.05. The results showed that the Hurst indices of each two-hour are all greater than 0.5. The three highest Hurst indices were: Stomach Hurst (0.960) ＞ Heart Hurst (0.946) ＞ Spleen Hurst (0.945), and the three lowest Hurst indices were: Lung Hurst (0.886) ＜ Liver Hurst (0.893) ＜ Large intestine Hurst (0.905). The standard deviation of the large intestine Hurst was the largest, reaching 0.088, and the standard deviation of the gastric Hurst was the smallest, 0.058. The distribution image of the Hurst index of individual patients at each twohours was similar to that obtained by the whole sample, but the specific time to a certain two-hours had fluctuations. The number of pairs with statistical difference between each two groups in two-hours is 29, accounting for 44％ of the total number of pairs. The organs and meridians that have more differences with other two-hours are successively stomach, lung, liver, kidney, spleen and heart. The differences of the blood glucose changes at different times in patients with type 2 diabetes can be indicated by the dynamic blood glucose Hurst indices, which are calculated according to the rule of Qi and blood flow.