[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis].

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

[Analysis of the diagnosis and treatment of 24 cases of hepatic perivascular epithelioid cell tumor].

Objective: To investigate hepatic perivascular epithelioid cell tumor (PEComa) diagnosis and treatment plan. Methods: 24 cases diagnosed with PEComa clinical manifestations, serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), imaging findings, surgical methods, postoperative hospital stay, pathological results and prognosis were analyzed retrospectively from September 2015 to September 2020. Results: Majority of patients were females (79.2%), aged 41.5±11.4 years. Tumors were predominantly located in the right liver (50.0%). 76.7% of the cases were mostly clinically asymptomatic. AFP, CEA and CA199 indices were all negative. CT mostly showed low density tumor in the plain scan phase, enhanced in the enhancement phase, and enhanced and weakened in portal venous and equilibrium phase (66.7%). MRI manifestations of most tumors were hypointense on T1WI and hyperintense on T2WI (72.7%). B-ultrasound mostly showed hyperechoic mass in the tumor area with punctate vascular shadow (52.9%). Postoperative hospital stay was 9.0±2.4 days for laparoscopic surgery patients (n=13), 13.4±6.3 days for traditional laparotomy (hereinafter referred to as laparotomy, n=10), and 3 days for 1 patient with microwave ablation. All postoperative pathological results were positive for HMB45 and Melan-A. Follow-up results: 21 cases survived normally, with no tumor recurrence in the recent physical examination; two cases had tumor recurrence and they died two and three years after surgery, and one case was lost to follow-up. Conclusion: Hepatic PEComa more commonly occurs in middle-aged women, with no specific features for tumor markers and clinical manifestations. Some imaging findings are specific, so its features can be combined as a basis for diagnosis. Postoperative pathological examination results can confirm the diagnosis. Therefore, surgery remains the initial treatment plan. Microwave ablation and laparoscopic surgery are recommended as the preferred option because of shorter hospital stays and less trauma than open surgery.

[Incidence and risk factors of metabolic syndrome in rural community population on islands in Zhejiang province].

Objective: To estimate the incidence of metabolic syndrome and explore possible risk factors for metabolic syndrome in adults of rural communities in Yuhuan county, Zhejiang province, China. Methods: During June-December, 2018, a follow-up survey was conducted in participants without metabolic syndrome at baseline survey in 2012 to obtain the information collected in questionnaire survey, anthropometric data and laboratory data. The incidence of metabolic syndrome in the participants was estimated, and Logistic regression model was used to explore the risk factors, adjusted risk ratio (aRR) and 95%CI. Results: Among 3 162 participants, 522 new metabolic syndrome cases were identified. The 6-year cumulative incidence rate of metabolic syndrome was 16.5%, and the cumulative incidence rate was higher in women (20.6%) than that in men (12.3%, P<0.001). Those incidence rates were higher in those in jobless, smoking or drinking groups. Being women (aRR=1.96, 95%CI: 1.50-2.58) and family history of hypertension (aRR=1.31, 95%CI: 1.04-1.63) were independent risk factors for metabolic syndrome. Conclusion: The follow up indicated that the incidence of metabolic syndrome was relatively high in rural adults on islands in Zhejiang, and women or those with family history of hypertension were more likely to have metabolic syndrome.

[Structural Analysis of the 5'-Flanking Region of Human Alpha-Fetoprotein Encoding Gene].

Alpha fetoprotein (AFP) is a growth factor and a signaling molecule that promotes the development of HCC. However, the mechanism of the awakening of AFP in course of HCC progression remains unclear. We have studied the structure of AFP 5'-flanking regulatory sequence using dual-luciferase reporter vectors with fragments of this region. Reporter constructs were transfected into HepG2 and PLC hepatoma cell lines. The AFP 5'-flanking regulatory sequence between -1871 and -1004 bp was promoting gene transcription, while the effects of the sequence between -1004 and -667 bp were small. The fragment located between positions -667 and -448 bp inhibited the transcriptional activity of the AFP gene, while the fragment located between -448 and -287 bp promoted expression of AFP. The effects of the adjacent promoter sequence were small. A variety of transcription factor binding sites were mapped.

Regulation of HBV replication and gene expression by miR-501-3p via targeting ZEB2 in hepatocellular carcinoma.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.

WITHDRAWN: LncRNA-LINC00261 suppresses the progression of NSCLC cells through upregulating miR-19a-mediated Kruppel-like factor 2 (KLF2).

Ahead of Print article withdrawn by publisher.

[Diagnosis and treatment of pancreatic tuberculosis: experiences of 10 cases].

Objectives: To study the clinical characteristics of pancreatic tuberculosis, and therefore to improve the diagnosis and treatment of this disease. Methods: The clinical data of 10 patients with pancreatic tuberculosis form 1990 to 2017 were reviewed, including clinical characteristics, laboratory tests and imaging features. Results: The ten patients aged 28 to 71 (median 56) years. All of them presented varying degrees of abdominal pain and weight loss (3 to 8 kg). Hypo-echoic pancreatic masses were shown by abdominal ultra-sound in 7 cases, and cystic-solid masses with thick wall was shown by abdominal CT scan in 4 cases, but dilatation of the pancreatic duct was found in none of the 10 cases. Hemoglobin levels lower than 12 g/L were found in 6 cases, and ESR more than 20 mm/1 h was present in 7 cases. Four cases received PPD test, but only one was positive. CA19-9 was found to be higher than normal (27 IU/ml) in 3 cases (39.2 IU/ml, 125.7 IU/ml, 88.9 IU/ml respectively). Three cases received T-spot.TB tests, and all the results were positive. Seven cases received laparotomy, and the other 3 received endoscopic ultrasound-guided biopsy. Caseous necrosis and Langerhans cells were found in all the 10 cases. Nine patients were treated by 6 to 12 months' anti-tuberculosis therapies, and at 1-5 years' follow-up, 8 were cured and 1 improved. Conclusions: The manifestations of pancreatic tuberculosis were easy to be confused with other diseases, and therefore a comprehensive understanding of history and careful examinations were important for a correct diagnosis. Once the diagnosis was made, prompt standard anti-tuberculosis therapy could lead to a favorable outcome.

[The epidemiological and clinical characteristics of liver hemangioma in health adults].

Objective: To report the epidemiological and clinical characteristics of liver hemangioma in health adults from a large sample of Health Examination Database. Methods: A retrospective study was performed to analyze the epidemiological and clinical Characteristics of liver hemangioma from people who underwent examination in China-Japan friendship hospital from 2014 to 2016. The analysis was also included the relationship between gender or age and the incidence and tumor size. Results: A total of 83 964 healthy adults (age≥18) were included in the study. The overall incidence of liver hemangioma was 2.95%. There was no significant difference of liver hemangiomas incidence between male which was 3.03%, and which was 2.88% in female. Liver hemangiomas incidence had shown obviously increased with patients' age, as the evidence indicating that the prevalence of liver hemangioma in <30 age group was only 1.87%, and the prevalence of liver hemangioma in 41-50 age group raised to 3.72%. While the size of liver hemangioma in different genders was also increasing with age, the tumor size of liver hemangioma in <30 age group was the smallest. Under 50 years old, the size of female patients' liver hemangioma was larger than that of male patients in each age group. The size of female patients' liver hemangioma had obviously decreased over 60 years old. Conclusion: The progress of liver hemangioma was highly influenced by age and gender.

Dexmedetomidine protects liver cell line L-02 from oxygen-glucose deprivation-induced injury by down-regulation of microRNA-711.

OBJECTIVE: In liver transplantation, long-time portal vein blocking causes the occurrence of ischemic liver injury. Dexmedetomidine, a widely admired anesthetic, has been reported as a protective agent on organs under ischemic condition. The objective of this study was to reveal the role and underlying mechanism of dexmedetomidine in ischemic liver injury. MATERIALS AND METHODS: L-02 cells were treated with dexmedetomidine during 6 h of oxygen-glucose deprivation (OGD) exposure. The expression of microRNA-711 (miR-711) in cell was overexpressed by miRNA transfection. Then, the following parameters were observed: cell viability, apoptosis, the expression of apoptosis-related proteins, and the expression and the release of Interleukin 1 beta (IL-1ß) and Tumor necrosis factor alpha (TNF-α). RESULTS: Apoptosis and inflammation were induced following OGD exposure in L-02 cells, as cell viability was impaired, apoptotic cell rate was increased, caspase-3, and caspase-9 was cleaved, and the expression and release of TNF-α and IL-1ß were increased. Dexmedetomidine attenuated OGD-induced apoptosis and inflammation, and dexmedetomidine down-regulated the expression of miR-711. Also, dexmedetomidine blocked the activation of p38 mitogen-activated protein kinase (p38MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signaling upon OGD. Moreover, when miR-711 was overexpressed, dexmedetomidine did not protect L-02 cells against OGD, and did not block p38MAPK and JAK/STAT signaling pathways. CONCLUSIONS: Dexmedetomidine ameliorated OGD-induced cell apoptosis and inflammation in L-02 cells, exerting protective activities in ischemic liver injury. The anti-OGD effects of dexmedetomidine might be realized by down-regulation of miR-711 and suppression of p38MAPK and JAK/STAT signaling pathways.

Hypoxia-induced apoptosis and mitochondrial dysfunction in chondrocytes arising from CREB phosphorylation reduction.

Chondrocytes, which are embedded within the growth-plate or the intervertebral disc, are sensitive to environmental stresses, such as inflammation and hypoxia. However, little is known about the molecular signaling pathways underlying hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes. We first examined the apoptosis, caspase-3 activity, and apoptosis-associated markers in human chondrocyte cell line C28/I2 under normoxia or hypoxia. We then investigated mitochondrial dysfunction and the activation of cyclic adenosine monophosphate response element-binding protein (CREB) signaling in the same human chondrocyte cell line. Our results indicated that hypoxia induced apoptosis and reduced CREB phosphorylation in chondrocytes. Upregulated mitochondrial superoxide and reactive oxygen species levels, and reduced mitochondrial membrane potential and complex IV activity were observed in hypoxia-treated C28/I2 cells. In conclusion, the present study confirmed reduced CREB phosphorylation, apoptosis induction, and mitochondrial dysfunction in the hypoxia-treated chondrocyte cells. This implies the key role played by CREB signaling in hypoxia-induced mitochondrial dysfunction and apoptosis in chondrocytes.

Interferon-ß efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis.

Neovascularization has a critical role in the growth and metastatic spread of tumors, and involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow. In this study, we examined whether EPCs could promote tumor angiogenesis, and found that the tumor growth was enhanced by the administration of EPCs. To test the hypothesis that genetically modified bone marrow-derived EPCs can be effective carriers of therapeutic agents to tumor sites, we conducted human interferon-beta (HuIFN-ß) gene transfection of EPCs with a virus vector in vitro. When HuIFN-ß was applied in the ex vivo culture of EPCs, HuIFN-ß-transduced EPCs achieved efficient killing of the total population of SPC-A1 cells, indicating a bystander effect was elicited by HuIFN-ß-transduced EPCs in vitro. When SCP-A1 cancer cells were coimplanted along with ex vivo cultivated EPCs subcutaneous injection in nude mice, the tumor growth was increased. However, the anti-tumor effect of interferon-beta (IFN-ß) offset the tumor-progressive character of EPCs and the tumor growth, and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon IFN-ß treatment. In addition, overall expression levels of vascular endothelial growth factor in tumor tissues were decreased upon IFN-ß treatment. Therefore, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system.

[Diagnosis and treatment of Sturge-Weber syndrome associated with retinal detachment].

OBJECTIVE: To access the diagnosis and treatment of Sturge-Weber syndrome at late stage. METHODS: The male patient aged 65 visited the eye clinic with presenting symptom of visual loss of the left eye for 2 months. Ocular examination disclosed a facial hemangioma with the size of 2 cm x 3 cm on the nasal side of the left upper eyelid associated with engorged bulbar conjunctival and episcleral vessels in the upper nasal quadrant. Ophthalmoscopy revealed total detachment of the retina. Esotropia was measured as 10 degrees. Intraocular pressure was 24 mmHg. Electroretinogram (ERG) demonstrated an indistinguished pattern. Posterior trans-scleral and ciliary body cryocoagulation was applied followed by external release of the subretinal fluid. RESULTS: The retina became reattached with visual acuity of 0.3 and intraocular pressure was 15 mmHg of the left eye at 5 months postoperatively. Fluorescein angiographical findings were consistent with diffuse hemangioma of the choroid. Follow-up study for 6 years revealed that the retina remained attached with visual acuity of 0.8 and essentially normal electroretinogram. CONCLUSION: The small facial hemangioma was the clue for the diagnosis of Sturge-Weber syndrome and cryocoagulation was the procedure of choice for the treatment of retinal detachment with favorable visual outcome.

Effects of tanshinone II-A sulfonate on adhesion molecule expression of endothelial cells and platelets in vitro.

AIM: To study the action of tanshinone II-A sulfonate (Tan) on adhesion molecule expression by cultured endothelial cells and platelets. METHODS: Tumor necrosis factor alpha (TNF-alpha)-induced ICAM-1 expression on the cell surface and endothelial adhesivity toward HL-60 cells were studied using human umbilical vein endothelial cells (HUVEC). Thrombin-induced expression of platelet P-selectin was studied using human blood platelets. Adhesion molecule expression on the cell surface was measured by flow cytometry. The number of HL-60 cells adhering to the HUVEC monolayer was determined by liquid scintillation spectroscopy. RESULTS: Pretreatment of HUVEC with TNF-alpha significantly enhanced ICAM-1 expression and increased HL-60 cells adhesion to HUVEC from 4.6% +/- 0.7% to 30% +/- 6%. Tan (25-200 mumol.L-1) inhibited the effects of TNF-alpha in a concentration-dependent manner. Tan also inhibited the increase of P-selectin expression of thrombin-activated platelets in a concentration-dependent manner. CONCLUSION: Tan inhibited expression of adhesion molecules (ICAM-1, P-selectin) in HUVEC and in human blood platelets.