Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Thyroid cancer is caused by multiple factors, including genetics, environment, metabolism, and the immune microenvironment, among which ionizing radiation exposure is an important risk factor for thyroid cancer. As one of the most sensitive target organs of ionizing radiation, the thyroid gland may have different risks of thyroid cancer caused by different types of ionizing radiation exposures, such as medical exposure, occupational exposure, and emergency exposure. The sensitivity of children and adolescents are higher than that of adults. The dose-response relationship still needs to be further explored. The molecular mechanism between ionizing radiation and the increased risk of thyroid cancer is complex, which may involve DNA damage and repair abnormalities, gene mutations, non-coding RNA regulation, DNA methylation, cell cycle regulation imbalance, and immune microenvironment changes. This article reviews the risk and molecular mechanisms associated with different types of ionizing radiation exposure in thyroid cancer, based on literature retrieved from CNKI and PubMed databases. It aims to provide a theoretical basis for the early monitoring, prevention, and intervention of thyroid cancer related to ionizing radiation exposure.

Objective To investigate the value of cranial CT cisternal grading combined with D-dimer(D-D)and Glasgow Coma Scale(GCS)score in predicting the short-term postoperative prog-nosis of patients with severe traumatic brain injury.Methods A total of 165 patients with severe trau-matic brain injury who were treated in the hospital from January 2019 to May 2024 were selected as study subjects,all underwent craniotomy surgery.Postoperative follow-up was conducted for 3 months to analyze the differences in clinical data and preoperative indicators such as cranial CT cisternal grad-ing,D-D levels,and GCS scores between patients with poor and good prognosis.The value of cranial CT cisternal grading,D-D levels,and GCS scores in predicting short-term postoperative poor prognosis in patients with severe traumatic brain injury was also analyzed.Results Compared with patients with good prognosis,patients with poor prognosis had higher proportion of age,cranial CT cisternal grading of Ⅰ to Ⅱ,D-D levels,and GCS scores＜6(P＜0.05).There were no statistically significant differences in C-reactive protein,prothrombin time,activated partial thromboplastin time,international normalized ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol levels between patients with poor and good prognosis(P＞0.05).Cranial CT cisternal grading,D-D levels,and GCS scores were influencing factors for short-term postoperative poor prognosis in patients with severe traumatic brain injury(P＜0.05).The area under the curve for poor prognosis by three indicators in combination was 0.941(95％CI,0.906 to 0.975),which was higher than the area under the curve for the individual predictions of cranial CT cisternal grad-ing,D-D levels,and GCS scores(P＜0.05).Conclusion The influencing factors for short-term postoperative prognosis in patients with severe traumatic brain injury include cranial CT cisternal grading,D-D levels,and GCS scores.The model based on these three indicators has certain appli-cation value in predicting patient prognosis.

Objective To construct a swallowing dynamic model for simulating dysphagia caused by reduced tongue movement am-plitude.Methods A swallowing dynamic model was established based on medical imaging data from CT and videofluoroscopic swallowing study(VFSS).The finite element method was used to simulate soft tissues,while the smoothed parti-cle hydrodynamics method(SPH)was used to simulate bolus.The model's posture at each time point was com-pared with the imaging data of VFSS from twelve patients with dysphagia,and a normalization method was used for quantitative evaluation of the model's validity.By adjusting the tongue movement amplitude under different viscosity conditions,the role of tongue movement in the swallowing process was investigated,and the swallow-ing safety and efficiency were assessed.Results The tongue posture and bolus trajectory presented by the swallowing dynamic model were consistent with the VFSS imaging.The brightness in the epiglottis area in VFSS images correlated with the equivalent brightness of SPH particles in the simulation results(r=0.97).As the tongue movement amplitude reducing by 20%,the num-ber of aspirated particles,swallowing efficiency and the average velocity of bolus particles in the oropharyngeal cavity all performed well.Pudding-like fluids exhibited favorable swallowing characteristics even when tongue movement amplitude reducing significantly.Conclusion The swallowing dynamic model can simulate the human swallowing process,providing good support for re-habilitation training of patients with dysphagia and the development of specialized medical foods,demonstrating significant potential for clinical applications.

Objective To construct a swallowing dynamic model for simulating dysphagia caused by reduced tongue movement am-plitude.Methods A swallowing dynamic model was established based on medical imaging data from CT and videofluoroscopic swallowing study(VFSS).The finite element method was used to simulate soft tissues,while the smoothed parti-cle hydrodynamics method(SPH)was used to simulate bolus.The model's posture at each time point was com-pared with the imaging data of VFSS from twelve patients with dysphagia,and a normalization method was used for quantitative evaluation of the model's validity.By adjusting the tongue movement amplitude under different viscosity conditions,the role of tongue movement in the swallowing process was investigated,and the swallow-ing safety and efficiency were assessed.Results The tongue posture and bolus trajectory presented by the swallowing dynamic model were consistent with the VFSS imaging.The brightness in the epiglottis area in VFSS images correlated with the equivalent brightness of SPH particles in the simulation results(r=0.97).As the tongue movement amplitude reducing by 20%,the num-ber of aspirated particles,swallowing efficiency and the average velocity of bolus particles in the oropharyngeal cavity all performed well.Pudding-like fluids exhibited favorable swallowing characteristics even when tongue movement amplitude reducing significantly.Conclusion The swallowing dynamic model can simulate the human swallowing process,providing good support for re-habilitation training of patients with dysphagia and the development of specialized medical foods,demonstrating significant potential for clinical applications.

Objective:To investigate the effect of conventional treatment plus long-term transcranial direct current stimulation (tDCS) on consciousness recovery in patients with minimally conscious state (MCS) after traumatic brain injury (TBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 60 patients with MCS after TBI admitted to Zhejiang Armed Police Corps Hospital from January 2019 to December 2020, including 38 males and 22 females, aged 19-60 years [(45.7±11.4)years]. Course of disease was 3-6 months [(4.6±0.9)months]. Of all, 30 patients received internal medicine, hyperbaric oxygen, rehabilitation and other conventional treatment (conventional treatment group), and 30 patients received tDCS stimulation on the basis of conventional treatment (tDCS treatment group). The tDCS stimulation contained 4 cycles for 28 days with each cycle lasting for 7 days (stimulation for 5 days, rest for 2 days). Coma recovery scale-revised (CRS-R) total score, brainstem auditory evoked potential (BAEP) score and clinical effictive rate (significantly effective+effective) were compared between the two groups before treatment, during 4 cycles of treatment and at 6 months and 12 months after treatment. Complications induced by tDCS were also evaluated.Results:There was no significant difference in CRS-R total score and BAEP score between the two groups before treatment (all P>0.05). CRS-R total score and BAEP score in tDCS treatment group were significantly higher than those in conventional treatment group during 4 cycles of treatment and at 6 months and 12 months after treatment (all P<0.05). CRS-R total score and BAEP score in both groups gradually increased during 4 cycles of treatment and at 6 months and 12 months after treatment (all P<0.05). The clinical effective rate in tDCS treatment group was 73% (22/30) when compared to 57% (17/30) in conventional treatment group ( P<0.05). In tDCS treatment group, 10 patients had local reversible slight redness at the cathodal position, while no other serious adverse effects, such as local burns, ulceration, exudation or epilepsy. Conclusion:Compared with conventional treatment, conventional treatment plus long-term tDCS can be more effective in improving the state of consciousness without serious adverse effects for MCS patients after TBI.

Objective: Abnormalities of static brain activity have been reported in schizophrenia, but it remains to be clarified the temporal variability of intrinsic brain activities in schizophrenia and how atypical antipsychotics affect it. Methods: We employed a resting-state functional magnetic resonance imaging (rs-fMRI) and a sliding-window analysis of dynamic amplitude of low-frequency fluctuation (dALFF) to evaluate the dynamic brain activities in schizophrenia (SZ) patients before and after 8-week antipsychotic treatment. Twenty-six schizophrenia individuals and 26 matched healthy controls (HC) were included in this study. Results: Compared with HC, SZ showed stronger dALFF in the right inferior temporal gyrus (ITG.R) at baseline. After medication, the SZ group exhibited reduced dALFF in the right middle occipital gyrus (MOG.R) and increased dALFF in the left superior frontal gyrus (SFG.L), right middle frontal gyrus (MFG.R), and right inferior parietal lobule (IPL.R). Dynamic ALFF in IPL.R was found to significant negative correlate with the Scale for the Assessment of Negative Symptoms (SANS) scores at baseline. Conclusion Our results showed dynamic intrinsic brain activities altered in schizophrenia after short term antipsychotic treatment. The findings of this study support and expand the application of dALFF method in the study of the pathological mechanism in psychosis in the future.

OBJECTIVETo evaluate the clinical application of carbon nanoparticles labeled lymph node staining in curative laparoscopic resection for colorectal carcinoma.

METHODSSixty-five patients undergoing curative laparoscopic resection for colorectal carcinoma in the Sun Yat-sen Memorial Hospital between September 2011 and June 2013 were prospectively enrolled and randomly divided into label group (with carbon nanoparticles, n=34) and control group (without carbon nanoparticles, n=31). Association between labeled lymph nodes and metastasis was analyzed. The total number of retrieved lymph nodes and lymph nodes metastatic ratio were compared between the two groups.

RESULTSMean number of retrieved lymph node of the label group was higher as compared to the control group (22.3±4.2 vs. 15.4±3.5, P<0.05). The total number of retrieved lymph node was 725 in the label group and 478 in the control group. Among them, lymph node < 5 mm accounted for 4.6% (33/725) in the label group, which was higher than 2.0% (10/478) (P=0.025) in the control group. The number of black stain label lymph node was 412, with black stain ratio 56.8% (412/725) in the label group. Metastatic ratio of black stain nodes was significantly higher than that of non-stain nodes [28.6% (118/412) vs. 19.5% (61/313), P=0.005].

CONCLUSIONSThe technique of carbon nanoparticles labeled lymph node staining in curative laparoscopic resection for colorectal carcinoma is easy and effective, which can increase the retrieved number of lymph nodes, especially for nodes < 5 mm. The black stain lymph nodes indicate higher risk of metastasis.

Objective This study aimed to explore the clinical value of human papilloma virus ( HPV) E6/E7 mRNA tests in identifying precancerous lesions of the uterine cervix-cervical intraepithelial neoplasia 2 or more CIN2+( CINⅡand CINⅢ).Methods This study is a cross-sectional survey design , between December 2011 to December 2013.The specimens were collected from the First People′s Hospital of Huizhou and the Third People′s Hospital of Huizhou in Department of Obstetrics and Gynecology outpatient and inpatient of cervical disease suspected patients , with thin-prep cytologic test ( TCT ) and histopathological results as reference , detected 345 patients of exfoliated cervical epithelial cells by using the branched DNA (b-DNA) technology to evaluate the application value of high risk HPV E 6 /E7mRNA in the clinical diagnosis of CIN.Using spss 19.0 software for data analysis.Results (1)Compared with TCT, the positive rate of E6/E7 mRNA in 325 samples were grading by cytology as follows: no intraepithelial lesion cells (NILM) 21.1%(40/190), atypical squamous cells (ASC) 38.5%(15/39 ), low-grade squamous intraepithelial lesions ( LSIL ) 76.9% ( 30/39 ) , atypical squamous cells can not exclude high-grade intraepithelial lesions (ASC-H) (8/10), high-grade squamous intraepithelial lesions (HSIL) 72.3%(34/47), TCT grades and HPV E6/E7 mRNA positive rate showed linear association (χ2 =67.654,P<0.01;r=0.497, P<0.01 ); and with HPV E6/E7 mRNA copy number was also relevant ( r =0.511, P <0.01).(2) Compared with pathological results , the positive rate of E6/E7 mRNA in 164 women samples were grading by pathology as follows:with NILM was 27.8%(10/36), with CIN Ⅰwas 65.9%(29/44), with CINⅡwas 80.6%(54/67), and with CINⅢwas 82.4%(14/17), pathological grades and HPV E6/E7 mRNA positive rate showed a linear correlation (χ2 =26.426, P<0.01; r=0.438, P<0.01); and the number of copies correlated with the increase of pathological grades too (r=0.543, P<0.01).(3) Screening effectiveness analysis results showed , the sensitivity of HPV E6 /E7mRNA was 84.6% while TCT was 47.7%.The sensitivity and specificity were 40.0% and 91.1% respectively when HPV E6/E7 mRNA and TCT processed as sequential detection test.The CIN2 +( CINⅡand CIN Ⅲ) best diagnostic critical point of 890.26 copies/ml,was established using receiver operating characteristic ( ROC) curve.The sensitivity and specificity were 58.5% and 93.7%, respectively.Conclusions The sensitivity of HPV E6/E7 mRNA test is better than TCT, the specificity is high in HPV E6/E7 mRNA and TCT processed as sequential detection test.Using the optimal cut-off value of ROC curve to detect CIN 2+has high sensitivity and specificity, so the detection of HPV E6/E7 mRNA may have some clinical value in screening and risk assessment of precancerous lesions of the uterine cervix.

Objective To evaluate the clinical application of carbon nanoparticles labeled lymph node staining in curative laparoscopic resection for colorectal carcinoma. Methods Sixty-five patients undergoing curative laparoscopic resection for colorectal carcinoma in the Sun Yat-sen Memorial Hospital between September 2011 and June 2013 were prospectively enrolled and randomly divided into label group (with carbon nanoparticles, n=34) and control group (without carbon nanoparticles, n=31). Association between labeled lymph nodes and metastasis was analyzed. The total number of retrieved lymph nodes and lymph nodes metastatic ratio were compared between the two groups. Results Mean number of retrieved lymph node of the label group was higher as compared to the control group (22.3± 4.2 vs. 15.4±3.5, P<0.05). The total number of retrieved lymph node was 725 in the label group and 478 in the control group. Among them, lymph node < 5 mm accounted for 4.6%(33/725) in the label group, which was higher than 2.0%(10/478) (P=0.025) in the control group. The number of black stain label lymph node was 412, with black stain ratio 56.8%(412/725) in the label group. Metastatic ratio of black stain nodes was significantly higher than that of non-stain nodes [28.6%(118/412) vs. 19.5%(61/313), P=0.005]. Conclusions The technique of carbon nanoparticles labeled lymph node staining in curative laparoscopic resection for colorectal carcinoma is easy and effective , which can increase the retrieved number of lymph nodes, especially for nodes < 5 mm. The black stain lymph nodes indicate higher risk of metastasis.