[Application of serum SAA, CRP, PCT, WBC and N% in the diagnosis of neonatal septicemia].

To explore the application value of SAA (serum amyloid A), CRP (C reactive protein), PCT (procalcitonin), WBC (white blood cell) and N% (neutrophil %) in the diagnosis of neonatal septicemia. This study was a retrospective study. 173 children with clinically diagnosed septicemia and 66 children with definitely diagnosed septicemia admitted to the Department of Neonatology, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China,from January 2022 to January 2024 were selected as the case group, and 148 children with neonatal jaundice who were hospitalized during the same period were selected as the control group. Fasting venous blood was collected within 24 hours after the children's admission to detect the levels of serum WBC, N%, SAA, CRP and PCT. One-way analysis of variance and Kruskal-Wallis H test were used to compare the general data and inflammatory index levels of the three groups of children. The correlation analysis between SAA and other inflammatory indicators was conducted using Spearman correlation analysis. The receiver operating characteristic (ROC) curve was used to determine the diagnostic efficacy of different inflammatory indicators for patients with definitely diagnosed septicemia and those with clinically diagnosed septicemia, and for those with clinically diagnosed septicemia and those without infection. The results showed that the levels of WBC [(16.88±5.64)×109/L], N% [70.00 (63.00, 75.00)], PCT [2.22 (1.20, 5.55) mg/L], CRP [3.00 (0.50, 10.30) mg/L], SAA [19.70 (10.82, 49.90) mg/L] in the clinically diagnosed septicemia group and WBC [(16.10±7.48)×109/L], N% [73.50 (61.50, 80.93)], PCT [5.35 (0.69, 20.07) mg/L], CRP [15.52 (4.98, 30.50) mg/L], SAA [43.95 (14.00, 175.98) mg/L] in the definitely diagnosed septicemia group were all higher than those in the control group (11.17±3.38)×109/L, 49.81 (36.93, 62.75), 0.20 (0.07, 0.99) mg/L, 0.54 (0.20, 1.40) mg/L, 5.15 (3.60, 8.68) mg/L, and the differences were all statistically significant (all P<0.05). Spearman correlation analysis showed that the level of SAA was positively correlated with WBC, N%, PCT and CRP (rs=0.453, 0.540, 0.343, 0.550, all P<0.05). ROC curve analysis showed that the area under ROC curve(AUC) of SAA for the definitely diagnosed septicemia group and the clinically diagnosed septicemia group was higher than that of other inflammatory indicators, among them, the AUC of SAA for diagnosing the definitely diagnosed neonatal septicemia group was 0.933 (95%CI: 0.809-1.000, P<0.05), with a sensitivity of 92.90% and a specificity of 99.30%. The AUC of SAA for diagnosing the clinically diagnosed septicemia group was 0.861 (95%CI: 0.818-0.904, P<0.05), with a sensitivity of 83.20% and a specificity of 81.80%. In conclusion, compared with CRP, PCT, WBC and N%, SAA has higher sensitivity and specificity for distinguishing neonatal septicemia (including definitely diagnosed septicemia and clinically diagnosed septicemia), and has certain auxiliary diagnostic value for neonatal septicemia.

[Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma].

Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

[Risk factors analysis and prediction model establishment of contralateral central lymph node metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma].

Objective: To explore the risk factors of contralateral central lymph nodes (Cont-CLNs) metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma and establish a prediction model. Methods: The clinical data of 206 patients receiving thyroid cancer surgery at Nantong University Affiliated Hospital between January 2021 and June 2023 were retrospectively analyzed, including 50 males and 156 females, with an age of [M(Q1, Q3)] 49.0(33.8, 57.0) years old. The risk factors of Cont-CLNs metastasis were screened by univariate analysis and multivariate logistic regression analysis. A nomogram was constructed for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC. The area under the receiver operating characteristic (ROC) curve(AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the model's predictive ability, accuracy, and clinical applicability, respectively. R language was used to randomly select 70% of the patients to establish a validation group for internal validation of the model. Results: Patients were divided into a metastasis group (n=56) and a non-metastasis group (n=150) based on the occurrence of Cont-CLNs metastasis. The ages of the two groups were 39.0 (28.0, 56.8) years and 51.0 (38.8, 57.0) years, respectively. There were statistically significant differences in gender, maximum tumor diameter (>1 cm), ipsilateral central lymph nodes (Ipsi-CLNs) metastasis, number of Ipsi-CLNs metastases (≥4), and lateral lymph node metastasis and Cont-CLNs metastasis between the two groups (all P<0.05). The results of multivariate logistic regression analyses showed that males(OR=2.926, 95%CI: 1.063-8.051), maximum tumor diameter>1 cm(OR=4.471, 95%CI: 1.344-14.877), and number of Ipsi-CLNs metastases≥4 (OR=5.011, 95%CI: 1.815-13.834) were risk factors for Cont-CLNs metastasis (all P<0.05). The AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model in the modeling group were 0.821 (95%CI: 0.744-0.898), 82.5%, and 63.4%, respectively. In the internal validation group, the AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model were 0.810 (95%CI: 0.717-0.902), 63.3%, and 83.7%, respectively. The calibration curves of the modeling group and the validation group showed that the model had good calibration ability. The DCA curves of the modeling group and the validation group indicated that the prediction model had good clinical adaptability. Conclusions: The prediction model constructed in this study has good predictive performance for Cont-CLNs metastasis in intermediate-to-high uPTC. When patient with intermediate-to-high risk uPTC is male, with maximum tumor diameter>1 cm, and the number of Ipsi-CLNs metastases≥4 should be alert to Cont-CLNs metastasis, and bilateral central lymph node dissection may be considered.

[Current situation of surgical treatment of gallbladder polyps and some problems that should be paid attention to].

Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.

[Overexpression of CDHR2 inhibits proliferation of breast cancer cells by inhibiting the PI3K/Akt pathway].

OBJECTIVE: To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway. METHODS: Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients. Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer. CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting. Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid, and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay, EdU assay, and cell cycle assay; the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting. RESULTS: Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them (P > 0.05), but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis. Immunohistochemistry, qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells (P < 0.01), and its overexpression strongly inhibited cell proliferation, caused cell cycle arrest, and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1. CONCLUSION: Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

Retraction Note: MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.

The article "MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6", by W. Pan, L.-J. Pang, H.-L. Cai, Y. Wu, W. Zhang, J.-C. Fang, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3719-3725-DOI: 10.26355/eurrev_201905_17797-PMID: 31114997 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer regarding a possible manipulation in Figures 2 and 3, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive. The journal investigation revealed duplications in panels miR-1294 mimic - Caki01 and Caki01 of Figure 2D and in the Western blots of Figure 3 with previously published articles. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17797.

[Effects of Rhodiola rosea injection on intrapulmonary shunt and blood IL-6 and TNF-α levels during single lung ventilation in patients undergoing radical resection of esophageal cancer].

OBJECTIVE: To explore the effects of Rhodiola rosea injection on pulmonary shunt and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during single lung ventilation in patients undergoing radical resection of esophageal cancer. METHODS: Forty-six patients undergoing radical operation for esophageal cancer were randomized equally into control group and Rhodiola rosea injection group. In the Rhodiola group, 10 mL of Rhodiola rosea injection was added into 250 mL of normal saline or 5% glucose solution for slow intravenous infusion, and normal saline of the same volume was used in the control group after the patients entered the operation room. At T0, T1 and T3, PaO2 of the patient was recorded and 2 mL of deep venous blood was collected for determination of serum TNF-α and IL-6 levels. The incidence of postoperative atelectasis of the patients was recorded. RESULTS: Compared with those in the control group, the patients receiving Rhodiola rosea injection had significantly higher PaO2 and Qs/Qt at T1 and T2 (P<0.05) and lower serum IL-6 and TNF-α levels at T3 (P<0.05). No significant difference in the incidence of postoperative atelectasis was observed between the two groups (P>0.05). CONCLUSION: Rhodiola rosea injection before anesthesia induction can reduce intrapulmonary shunt during single lung ventilation, improve oxygenation, reduce serum IL-6 and TNF-α levels, and alleviate intraoperative lung injury in patients undergoing radical resection of esophageal cancer.

[Study on the inhibitory and pro-apoptotic effects of different concentrations of total tanshinone alone and in combination with tyrosine kinase inhibitors on human myeloid leukemia cell lines].

Objective: To explore the effect and investigate the molecular mechanism of different concentrations of total tanshinones alone and in combination with tyrosine kinase inhibitors (TKIs) on the proliferation inhibition and apoptosis of human myeloid leukemia cell lines. Methods: K562 and Kasumi-1 cell lines were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, and the TKIs-resistant strain K562/T315I cell line was constructed in Molecular Medicine Research Center, Beijing Lu Daopei Institute of Hematology. Logarithmic growth phase cells were taken and divided into intervention groups with total tanshinone of 0, 2.19, 4.38, 8.75, 17.50 and 35.00 µg/ml intervention groups, which were inoculated in 96-well plates at a density of 1×104 cells/well and exposed to the drug for 24 h, and a control group treated with dimethyl sulfoxide was also set up simultaneously. All experiments were repeated independently 3-5 times. The proliferative activity of the cells was assessed using the CCK-8 assay, the apoptotic rates were measured by flow cytometry, and the expression levels of apoptosis-regulating proteins Bcl-2 and Bax were analyzed by Western blotting. The cell lines treated and untreated with total tanshinone were subjected to transcriptome sequencing and gene set enrichment analysis to identify differentially expressed genes. Results: The half-inhibitory concentration (IC50) values of 8.75 µg/ml total tanshinone at 24 h for K562, K562/T315I and Kasumi-1 cells were (4.11±0.02), (4.95±0.04) and (3.98±0.01) µg/ml, respectively. When combined with 0.25 µmol/L imatinib, 8.75 µg/ml total tanshinone could enhance the induction of apoptosis effects on K562 and K562/T315I cell lines. After being treated with 4.38, 8.75, and 17.50 µg/ml of total tanshinone for 24 h, compared with the control group, total tanshinone upregulated the expression level of Bax protein, downregulated the expression level of Bcl-2 protein, and decreased the Bcl-2/Bax ratio (all P<0.05). Total tanshinone inhibited the proliferation-related signaling pathway and DNA damage repair pathway of myeloid leukemia cell lines, and activated the signaling pathway that induces apoptosis in leukemia cells. Conclusion: Different concentrations of total tanshinoneinhibites proliferation and promote apoptosis in K562, Kasumi-1 and TKIs-resistant K562/T315I cell lines, and further enhance the anti-leukemic effect when combined with TKIs.

[Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients].

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM (P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM (P=0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

[Effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery].

Objective: To investigate the effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery. Methods: This study was a cross-sectional study. Patients who underwent surgery for papillary thyroid cancer (PTC) at the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University between January 2022 and September 2023 were included. All patients underwent thyroid lobectomy or total resection, and central lymph node dissection was performed at the same time. During the operation, tracing injection of mitoxantrone hydrochloride and 785 nm and 660 nm dual fluorescence imaging technique were used to measure the fluorescence intensity (FI) of parathyroid glands, central lymph nodes and background. After correcting to obtain the standardized FI, the paired t-test was used to compare the standardized FI of the parathyroid glands and central lymph nodes, and the Spearman's rank correlation analysis was used to analyze the relationship between the standardized FI and various clinical indicators. Results: The study included 30 patients (8 males and 22 females), with a mean age of (41.8±10.4) years. A total of 76 parathyroid glands and 234 central lymph nodes were identified under dual fluorescence imaging, and the standardized FI of parathyroid glands was less than that of central lymph nodes (44.7±16.8 vs 99.5±28.4, P<0.001). The visualization rate, false rate and miscut rate of parathyroid glands under 785 nm wavelength excitation light were 98.7% (76/77), 0 (0/77) and 1.3% (1/77), respectively (one case with no visualization and miscutting parathyroid gland was the encapsulated type). The visualization rate of central lymph nodes under 660 nm wavelength excitation light was 98.7% (234/237). There was no significant correlation between FI and clinical indicators such as gender, age, height, weight, body mass index, preoperative thyroid stimulating hormone, thyroglobulin antibody, thyroid microsomal antibody, serum calcium, parathyroid hormone level and surgical procedure (all P>0.05). Conclusion: Dual fluorescence imaging of central lymph nodes and parathyroid glands can improve the ability to identify parathyroid gland while assisting central lymph node dissection.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

Multimodel habitats constructed by perfusion and/or diffusion MRI predict isocitrate dehydrogenase mutation status and prognosis in high-grade gliomas.

AIM: To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). CONCLUSIONS: The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.

Brusatol attenuated proliferation and invasion induced by KRAS in differentiated thyroid cancer through inhibiting Nrf2.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) can be developed from differentiated thyroid cancer, and this dedifferentiated transformation leads to poor prognosis and high mortality. The role of Nrf2 in the dedifferentiation of differentiated thyroid cancer (DTC) induced by KRAS remains unclear. METHODS AND MATERIALS: In this study, two DTC cell lines, BCPAP and WRO, were used to evaluate the function of Nrf2 in the dedifferentiation caused by wild-type KRAS (KRAS-WT) and G12V point mutation KRAS (KRAS-G12V). RESULTS: The overexpression of KRAS-WT and KRAS-G12V increased the proliferative and invasive ability of BCPAP and WRO cells. Aggressive morphology was observed in KRAS-WT and KRAS-G12V overexpressed WRO cells. These results suggested that overexpression of KRAS-WT or KRAS-G12V may induce dedifferentiation in DTC cells. The expression of Nrf2 was increased by KRAS-WT and KRAS-G12V in DTC cells. In addition, compared with normal thyroid tissues, the expression of Nrf2 protein was considerably higher in thyroid cancer tissues on immunohistochemistry (IHC) staining, and the increased expression of Nrf2 indicated a poor prognosis of thyroid cancer. These results indicated that Nrf2 is the KRAS downstream molecule in thyroid cancer. Functional studies showed that the Nrf2 inhibitor Brusatol counteracted the proliferative and invasive abilities induced by KRAS-WT and KRAS-G12V in BCPAP and WRO cells. In addition, the xenograft assay further confirmed that Brusatol inhibits tumor growth induced by KRAS-WT and KRAS-G12V. CONCLUSION: Collectively, this study suggests that Nrf2 could be a promising therapeutic target in KRAS-mediated dedifferentiation of thyroid cancer.

[Effects of three-dimensional computed tomography angiography-assisted free medial sural artery perforator flap in repairing foot wounds].

Objective: To investigate the effects of three-dimensional computed tomography angiography (3D-CTA)-assisted free medial sural artery perforator flap in repairing foot wounds. Methods: A retrospective observational study was conducted. From May 2018 to August 2021, 18 patients with foot soft tissue defects who met the inclusion criteria were admitted to the Department of Spine and Trauma Orthopedics of the Yidu Central Hospital of Weifang, including 13 males and 5 females, aged 19 to 55 years, with a wound area of 4.0 cm×3.0 cm-9.0 cm×8.0 cm at admission. Before the operation, CT scanner was used to scan the area from the supracondylar femur to the middle segment of the fibula of patients, and the obtained data were extracted into the Mimics16.0 software and analyzed to determine the pre-selected perforator, and then the image data of the pre-selected perforator side were analyzed further, and the body surface projection position of the perforating point of the medial sural artery in the calf region was marked. Based on the above examination, the flap was designed and cut according to the shape and area of the patient's foot tissue defect, and the area of flaps ranged from 5.0 cm×4.0 cm to 10.0 cm×9.0 cm. The donor sites were sutured directly or covered by skin grafting. The type of perforator, the diameters of perforator at the beginning and outlet point, and the location of the outlet point of perforator of the medial sural artery were observed under 3D-CTA examination before operation and compared to see if they were consistent with the observation under intraoperative condition. The survival of the flaps after operation was recorded. During follow-up, the satisfaction of patients with the wound repair effects, the sensory recovery of the recipient flaps, the healing of the donor wound, and whether there were complications affecting limb functions were recorded. Data were statistically analyzed with Kappa consistency test and equivalence test, and the 95% confidence intervals of measurement difference of perforator diameter and outlet point position of perforator were -0.50-0.50 mm and -2.0-2.0 cm, respectively. Results: The types of medial sural artery perforators observed during operation were type Ⅰ in 3 cases, type ⅡA in 6 cases, type ⅡB in 8 cases, and type Ⅲ in 1 case, which was consistent with the results of 3D-CTA before operation (Kappa=1.00, P<0.05). The blood vessel diameter detected by 3D-CTA before operation at the beginning of perforator of medial sural artery was (1.81±0.39) mm, and the blood vessel diameter at the outlet point of the perforator was (0.83±0.21) mm, which were close to the actual intraoperative measurement of (1.83±0.43) and (0.86±0.22) mm, respectively; equivalence test showed that the 95% confidence intervals of the measurement differences of diameter of medial sural artery perforator at beginning and outlet point were -0.18-0.22 and -0.08-0.14 mm, respectively, with both P values <0.05. The preoperative 3D-CTA detected that the perforating position at the deep fascia of the perforator of the medial sural artery, namely the vertical distance with the popliteal fold was (12.2±1.4) cm, and the horizontal distance with the posterior midline was (2.6±0.7) cm, which were respectively close to the actual intraoperative measurement of (12.4±1.4) and (2.6±0.7) cm; equivalence test showed that the 95% confidence intervals of the measurement differences in the vertical distance with the popliteal fold and the horizontal distance with the posterior midline of the outlet point of medial sural artery perforator were -1.06-1.26 and -0.46-0.66 cm, respectively, with both P values <0.05. After surgery, all flaps of 18 patients survived without vascular crisis. After 1 year of follow-up, the satisfaction degree of 16 patients was excellent and 2 patients was good with the wound repair effects, with a satisfaction ratio of 16/18; the sensory recovery of flap was evaluated as S3 in 11 cases and S2 in 7 cases; the donor wounds healed well without obvious scar or contracture, with no effect on limb joint functions. Conclusions: The medial sural artery perforator flap achieved good results in repairing foot wound with high degree of patient satisfaction. Preoperative application of 3D-CTA can realize the standardization, systematization, and visualization of artery perforator flap.

[Standardized and individualized treatment improves survival rate and quality of life for advanced thyroid cancer].

The overall prognosis of differentiated thyroid carcinoma is favorable, but some patients still progress to a locally advanced stage. At present, there are still some problems in the diagnosis and treatment of locally advanced thyroid cancer, which have not been completely clarified, and have caused some problems to the clinical treatment. This article provides a comprehensive analysis and elaboration on the selection of surgical methods for local advanced thyroid cancer, management of recurrent laryngeal nerve and trachea, timing selection of staging surgery, and targeted therapy, aiming at promoting standardized and individualized treatment for advanced thyroid cancer and improving the survival rate and quality of life.

[Preliminary analysis of neuroprotective effects of capillary fascia preservation recurrent laryngeal nerve anatomical method in right level â ¥ dissection].

Objective: To investigate the application and effect of capillary fascia preservation between the recurrent laryngeal nerve (RLN) and common carotid artery (fascia preservation method) in nerve protection when dissecting right level Ⅵ lymph nodes for patients with papillary thyroid carcinoma. Methods: A retrospective cohort study enrolling 195 patients with papillary thyroid carcinoma undergoing right level Ⅵ lymph node dissection in Beijing Tongren Hospital from March 2021 to August 2022 was carried out. The RLN was dissected by fascia preservation method in study group and by routine method in control group. The intraoperative electrical signal amplitude of the RLN, the number of dissected lymph nodes, and the postoperative complications were recorded and analyzed. Results: A total of 195 patients (study group: 94 cases, control group: 101 cases) were collected. There were 71 males and 124 females, with the median age of 32 (39, 51) years. In the study group, the total number of right level Ⅵ lymph nodes was significantly larger than the number of right Ⅵa level lymph nodes [8 (6, 11) vs 6 (4, 8), P<0.001]. There were no significant differences between the two groups in the number of level Ⅵa or level Ⅵb lymph nodes [Ⅵa: 6 (4, 8) vs 5 (3, 7), P=0.373; Ⅵb: 3 (1, 4) vs 2 (1, 4), P=0.337] and metastasis rate [Ⅵa: 51.1% (48/94) vs 52.5% (53/101), P=0.844; Ⅵb: 12.8% (12/94) vs 15.8% (16/101), P=0.541]. The ratio of electromyography (EMG) amplitude R2 in lower level Ⅵ and entry into larynx (grouped as>90%, 50%~90%,<50%) in the study group was significantly higher than that in the control group (P<0.001). No significant differences were detected between the two groups in temporary RLN paralysis [1.1% (1/94) vs 2.0% (2/101), P=1.000]. Conclusions: Fascia preservation method can decrease the stimulus and traction to RLN and preserve the capillary network serving RLN. It can thoroughly dissect lymph nodes and decrease the injury of RLN.

[Application of near-infrared autofluorescence imaging-based convolution neural network in recognition of parathyroid gland].

Objective: To investigate the application value of near-infrared autofluorescence imaging-based convolution neural network (CNN) for automatic recognition of parathyroid gland. Methods: The data of 83 patients who underwent thyroid papillary cancer surgery in the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University from August 2020 to March 2022 were retrospectively analyzed, and a total of 725 autofluorescence images of parathyroid gland were collected during the surgery. Meanwhile, non-parathyroid fluorescence imaging videos in the operation area of 10 patients were also collected, and 928 non-parathyroid fluorescence images were captured from those videos. The fluorescence images of parathyroid and non-parathyroid glands were directly used as input features for deep learning to construct ResNet 34, VGGNet 16 and GoogleNet models for automatic parathyroid identification. The ability of different models to identify parathyroid glands was tested by indicators such as accuracy, specificity, sensitivity, precision, receiver operating characteristic curve and area under the curve (AUC). In addition, 30 fluorescence images of parathyroid and 35 fluorescence images of non-parathyroid glands in 13 patients with papillary thyroid cancer from March to May 2022 were collected to prospectively test the best performing CNN model. Results: Among the 83 patients, there were 25 males and 58 females, with the mean age of (46.7±12.4) years. In the binary classification (parathyroid gland and non-parathyroid gland), the ResNet 34 model performed the best in different CNN models, the accuracy, specificity, sensitivity and precision of the identification test set were 97.6%, 96.3%, 99.3% and 95.5%, and the AUC reached 0.978 (95%CI: 0.956-0.991). In the prospective test, the prediction accuracy of the ResNet 34 model reached 93.8%, and the AUC was 0.938 (95%CI: 0.853-0.984). Conclusion: The near-infrared autofluorescence imaging-based deep CNN has good application value in the automatic recognition of parathyroid gland, and can be used to assist the recognition and protection of parathyroid gland in thyroid cancer surgery.

Adaptable polymerization platform for therapeutics with tunable biodegradability.

Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.