Intrahepatic cholangiocarcinoma(ICC)is a relatively rare type of primary liver cancer,and its incidence rate has gradually increased in recent years.Due to its insidious onset and atypical clinical symptoms,most patients are already in the advanced stage of the disease at the time of confirmed diagnosis,and therefore,timely diagnosis and treatment are of great importance.Radical surgical resection is the standard treatment regimen for early-stage ICC patients,while systemic chemotherapy is the basic treatment for patients with advanced ICC and is often combined with interventional treatment,targeted therapy,and immunotherapy.This article reviews the advances in the diagnosis and treatment of ICC.

Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Objective:To analyze the expression of silent information regulator 2-related enzyme 1 (SIRT1) and its relationship with chondrocyte apoptosis in patients with Kashin-Beck disease (KBD).Methods:Twenty patients with KBD were selected as the KBD group from Guide County, Qinghai Province, and 40 healthy subjects matched by age and sex were selected as the control group. Fasting elbow venous blood of the study subjects was collected, and peripheral blood mRNA levels of SIRT1 and selenoprotein genes [glutathione peroxidase (GPX) 2, GPX3, thioredoxin reductase (TXNRD) 1, TXNRD3, iodothyronine deiodinase Ⅰ (DIO1), and selenophosphate synthetase 2 (SPS2)] were detected by real-time PCR. The correlation between SIRT1 expression and selenoprotein genes in peripheral blood of KBD patients was analyzed by curve fitting method. Meanwhile, normal human chondrocytes cultured in vitro were divided into control group (without any treatment), resveratrol (RES) group (to verify the activation effect of RES on SIRT1), tert-butyl hydroperoxide (tBHP) injury group (oxidative injury model of chondrocyte), and RES protection group (tBHP injury after RES pre protection). The mRNA levels of SIRT1, selenoprotein genes, and apoptosis-related genes [B lymphoblastoma-2 gene (BCL2), BCL2-associated X protein (BAX), nuclear transcription factor κB (NF-κB) p65, and tumor suppressor gene P53] in each group of cells were detected by real-time PCR. Results:In the population study, the peripheral blood SIRT1 mRNA level in the KBD group (1.12 ± 0.38) was lower than that of control group (1.87 ± 0.97), and the difference was statistically significant ( t = 3.31, P = 0.002). According to curve fitting analysis, the mRNA levels of GPX3, TXNRD1, and TXNRD3 in peripheral blood of KBD group increased with the increase of SIRT1 mRNA level ( R2 = 0.48, 0.66, 0.95, P < 0.001). The level of DIO1 mRNA showed a trend of decreased first and then increased with the increase of SIRT1 mRNA level ( R2 = 0.51, P = 0.024). The mRNA levels of GPX2 and SPS2 showed no significant change trend with the increase of SIRT1 mRNA level ( R2 = 0.16, 0.12, P = 0.064, 0.114). In cell studies, compared with the control group (1.00 ± 0.10), the SIRT1 mRNA level in the RES group (1.79 ± 0.07) was higher ( P < 0.05). Compared with tBHP injury group, the RES protection group had higher mRNA levels of selenoprotein genes GPX3, TXNRD1, TXNRD3, and DIO1 ( P < 0.05); the mRNA levels of apoptosis-related genes BAX, P53 and the ratio of BAX/BCL2 were lower, while the mRNA levels of BCL2 and NF-κB p65 were higher ( P < 0.05). Conclusions:KBD patients have low expression of SIRT1. And RES activation of SIRT1 may enhance the antioxidant capacity of chondrocyte by up-regulating the expression of selenoprotein genes, thus inhibiting chondrocyte apoptosis.

Objective:To investigate the role of oxidative stress and silent information regulator 2 homolog 1 (SIRT1) in cartilage injury in Kashin-Beck disease (KBD) by evaluating the level of oxidative stress and the effect of oxidative injury on SIRT1 expression in patients with KBD.Methods:In May 2017, Twenty patients with KBD were selected from Guide County of Qinghai Province as the KBD group, and 40 healthy subjects were selected as the control group, 5 ml elbow venous blood was collected, centrifuged, and the upper plasma was retained. The glutathione peroxidase (GPX) activity and reactive oxygen species (ROS) level were determined by enzyme linked immunosorbent assay (ELISA), and SIRT1 mRNA level was determined by real-time fluorescence quantitative PCR (RT-qPCR). Meanwhile, 150 μmol/L tert-butyl hydroperoxide (tBHP) was selected to damage chondrocytes; and different concentrations of sodium selenite (Na 2SeO 3) were used to intervene in chondrocytes to detect cell viability, and appropriate concentration of Na 2SeO 3 was selected for pre protection. Total RNA and DNA of chondrocytes were extracted. The mRNA levels of SIRT1, DNA methyltransferase 1 (DNMT1), and the DNA methylation level in the SIRT1 promoter region were determined by RT-qPCR. At the same time, Hoechst 33342 staining was used to detect chondrocyte apoptosis. Results:The plasma GPX activity [(35.48 ± 8.82) U/g·Hb] in KBD group was lower than that in control group [(40.43 ± 6.68) U/g·Hb, t = - 2.43, P = 0.018], and the ROS level [(577.10 ± 96.92) U/ml] was higher than that in control group [(526.44 ± 62.63) U/ml, t = 2.13, P = 0.043]. GPX activity was positively correlated with SIRT1 mRNA level ( r s = 0.44, P = 0.005), while ROS level was negatively correlated with SIRT1 mRNA level ( r s = - 0.39, P = 0.006). After 48 hours of treatment with 150 μmol/L tBHP (tBHP injury group), the survival rate of chondrocytes decreased to (55.27 ± 2.96)%; and the survival rate of chondrocytes pre-protected with 0.10 μg/ml Na 2SeO 3 (selenium protection group) was significantly higher than that of tBHP injury group ( P < 0.05). Compared with control group, the SIRT1 mRNA level of chondrocytes in tBHP injury group was significantly decreased; while the DNA methylation level in the SIRT1 promoter region, DNMT1 mRNA level and cell apoptosis rate were significantly increased ( P < 0.05). Compared with tBHP injury group, the selenium protection group had higher levels of SIRT1 mRNA in chondrocytes, lower levels of DNA methylation in the SIRT1 promoter region, DNMT1 mRNA, and cell apoptosis rate ( P < 0.05). The apoptosis rate was negatively correlated with SIRT1 mRNA level ( r s = - 0.78, P = 0.004), and positively correlated with the DNA methylation level in the SIRT1 promoter region ( r s = 0.76, P = 0.006). Conclusions:KBD patients have increased levels of oxidative stress, which may be associated with low expression of SIRT1. Oxidative injury may down-regulate SIRT1 expression and promote chondrocytes apoptosis by catalyzing DNA methylation in the SIRT1 promoter region.

Objective: To understand the toxicological indexes and indexes factors of drinking water in rural schools in Yunnan Province during 2017-2020, so as to provide scientific basis for ensuring drinking water safety, and targeted intervention in rural schools. Methods: The end water of 456，399，391，387 rural primary and secondary school drinking water supply projects in 129 counties in Yunnan Province was collected from 2017 to 2020, 11 toxicological indexes were analyzed and evaluated. Results: The overall compliance rate of drinking water toxicological indexes in rural primary and secondary schools in Yunnan Province was 99.32 %; The top three indexes exceeding the standard were nitrate nitrogen(0.31%), chloroform (0.15%) and cadmium(0.09%). The difference of compliance rate by year was statistically significant( χ 2=11.04, P <0.05); No difference in compliance rate was found between dry and wet seasons( χ 2=0.05, P >0.05); The rate of the surface water meeting the standard was higher than that of the groundwater( χ 2=9.62, P <0.05). There was no significant difference in the compliance rate between the treated and untreated projects( χ 2=1.55, P >0.05); The daily water supply scale was less than 500 m 3, and the rate of reaching the standard was lower than that of daily water supply is greater than 500 m 3( χ 2=4.27, P <0.05). Conclusion The overall percentage of the toxicological indexes in drinking water exceeding the standard in rural primary and secondary schools in Yunnan Province is low. Nitrate nitrogen, chloroform and cadmium should be considered as the prioritirized pollutants of drinking water in rural schools of Yunnan Province.

Objective:To explore the experience of young cancer patients using mobile health applications, so as to provide a basis for improving the utilization rate and sustainability of health applications.Methods:From May to June 2020, purpose sampling was used to select 12 young cancer patients in the Internal Medicine Ward of a ClassⅢ Grade A cancer hospital in Nanjing, Jiangsu Province. The semi-structured interview with patients was conducted with the descriptive phenomenological method. The Colaizzi 7-step analysis method was used to analyze the data and refine the theme.Results:A total of four themes were summarized, namely, there was a difference in usage attitudes (being used for rehabilitation management, as a means of verification, generating resistance, and reducing the frequency of use) , insufficient function development and reduced user experience (lack of autonomy, insufficient intelligent evaluation) , desiring a professional operating agency, recognizing the development prospects and looking forward to perfection.Conclusions:In follow-up studies, researchers need to fully consider the patient's preference and usage habits for health applications on the basis of meeting the needs of disease management.

Inactivation of the skeletal muscle chloride channel ClC-1 results in myotonia congenita (MC), which occur with mutations of CLCN1 gene. However, there is no clear correlation between genotype and phenotype. Clinical data of a patient and his parents with MC were collected retrospectively, including the symptoms and signs, results of blood tests, electromyography, MRI images, and examination results of biceps brachii pathology by histopathology. The patient was diagnosed according to nextgeneration sequencing. Sanger sequencing was then carried out on his parents’ blood samples to verify their mutations. The patient had typical clinical characteristics of Becker myotonia with compound heterozygous mutations of the CLCN1 gene, inherited from his mother (M560T), who showed only mild symptoms and cold induced myotonic motor unit potentials, and from an unaffected father (c.697- 2delA on the intron 5 resulting in exon 6 skipping). In view of the compound heterozygous mutations, he could be classified into Becker myotonia congenita. In conclusion, these results suggested that CLCN1 mutations could lead to atypical myotonic symptoms and abnormities on electromyography (EMG). EMG after muscle cooling test and exercise tests should be completed in the relatives of patients with MC and some patients with atypical syndrome.

Objective To investigate the effect of time interval between diagnosis and surgical treatment on the prognosis of breast cancer.Methods A retrospective study that include a total of 252 female patients who underwent breast cancer diagnosis and treatment in the Second Affiliated Hospital of Xi'an Jiaotong University from April 2012 to August 2014 were included in the present study,the average age was (58.2 ± 10.8) years old,range from 31 to 67 years old.General demographic information and data of tumor were collected.Information on postoperative recurrence,metastasis,death,and disease-free survival status of breast cancer patients were followed up 5 years by outpatient follow-up or telephone follow-up.All participants were divided into four groups (＜2 weeks,2-4 weeks,4-8 weeks,≥8 weeks) by the time interval between diagnosis and surgical treatment,including 26,118,78 and 30 cases,respectively.In addition,according to the diameter of breast cancer tumors,all participants were divided into three groups (＜20 mm,20-40 mm,and ≥40 mm),including 99,124,and 29 cases,respectively.According to the results of pathological examination of the lymph nodes obtained during intraoperative dissection,the all participants were divided into three groups (lymph nodes without metastasis,1 to 3 metastasis,and ≥3 metastasis),including 66,124,and 62 cases,respectively.The Cox proportional regression risk models were used to assess the hazard ratio (HR) and its 95％ confidence interval (CI) of time interval between diagnosis and surgical treatment with the prognosis of breast cancer,with adjustment for age,education levels and body mass index.Further,stratified analysis by tumor characteristics,including pathological type,histological grade,tumor diameter,lymph node metastasis,and receptor expression were also conducted to evaluated the above association.Kaplan-Meier survival curve was used to evaluate the effects of time interval between diagnosis and surgical treatment on the prognosis of breast cancer.Results The Kaplan-Meier survival curves for the five-year follow-up of total survival time between 4 different time intervals groups showed significantly different (P ＜0.001),and patients with a pre-treatment interval of ＜2 weeks had the longest survival time,while those with ≥8 weeks had the lowest survival time.With a one-week interval before treatment,the overall risk of death in breast cancer patients increased by 6％ (HR =1.06,95％ CI:1.01-1.1 l),and the risk of breast cancer death increased by 8％ (HR =1.08,95％ CI:1.02-1.14),the risk of distant metastasis of breast cancer cells increased by 10％ (HR =1.10,95％ CI:1.08-1.13).With the increase in breast cancer tumor diameter (＜20 mm,20-40 mm,≥40 mm),the overall risk of death due to prolonged treatment interval increased gradually,with HR (95％CI) were 1.06 (1.03-1.09),1.08 (1.02-1.12) and 1.11 (1.05-1.17),respectively.With the increase of lymph node metastasis in breast cancer (no metastasis,metastasis at 1-3,≥ 3 metastasis),the total mortality risk caused by prolonged treatment time interval also showed an increasing trend,with HR (95％CI) were 1.04 (1.02-1.08),1.06 (1.04-1.08) and 1.08 (0.99-1.11),respectively.The same results were also shown in the effect of tumor diameter or distant lymph node metastasis on the association between treatment time interval and breast cancer survival and distant metastasis of breast cancer cells.Conclusion With the prolongation of the time interval between the diagnosis of the breast cancer and the surgical treatment of breast cancer patients,the risk of postoperative death is significantly increased,and the association is more pronounced in breast cancer patients with larger tumor volume or higher distant lymph node metastasis.

BACKGROUND: The tyrosine kinase inhibitors (TKI) treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation may have a positive effect, but most patients may develop drug resistance, therefore, the detection of the developing time in drug resistance and the research of the mechanism of drug resistance are need to be solved. While the emerge of next generation sequencing (NGS) have make it possible. The aim of this study is to monitor the efficacy of targeted therapy by studying the variation of circulating tumor DNA (ctDNA) mutation frequency and gene mutation spectrum through the targeted therapy. METHODS: Our center enrolled 22 patients with EGFR mutation detected by tissue or peripheral blood, and collect 8 mL of peripheral blood of the patients for ctDNA sequencing in different phases, before systematic prior treatment, followed-up by 2 months and disease progression after TKI administration. RESULTS: Patients with EGFR gene mutation may acquire a longer median survival time after receiving targeted drug therapy, due to the drop of mutation abundances, while the therapy may have a minor effect in patients which their mutation abundances have slightly decreased compared to the statistics before the cession (P=0.015,3). The significantly reduced group median progression was associated with a longer survival [progression free survival (PFS)=390 d]. At the same time, we found out that when related to TP-53 gene mutation, the effect of targeted drug therapy for EGFR-sensitive mutation was unsatisfactory (the median PFS was 120 d compared with 630 d, P=0.000,2). CONCLUSIONS Patients who has lower mutation abundance with EGFR sensitive mutations after TKI treatment may have a longer survival period (P<0.05), and the mutation abundance were not significantly dropping or accompanied by other mutations may indicating TKI resistance.