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.

Dent disease is a rare X-linked recessive renal tubular disease characterized by low molecular weight proteinuria，hypercalcemia and nephrocalcinosis. It is also a major cause of tubular proteinuria in children. According to different causative genes，Dent disease can be divided into three types：type 1 is caused by mutations in the CLCN5 gene，accounting for about 60%-70%；type 2 is caused by mutations in the OCRL gene，accounting for about 15%-20%；type 3 has a similar clinical phenotype but no known pathogenic gene mutations. CLCN5 encodes the voltage-dependent 2Cl -/1H +exchange channel CIC-5，which is involved in proximal renal tubule endocytosis. Its mutations can cause a variety of proximal tubular dysfunction symptoms，mainly including low molecular weight proteinuria. The use of gene detection technology has resulted in an increase in reports on Dent disease year after year. At present，the specific mechanism underlying Dent disease remains unknown. This article reviews the research progress of CLCN5，hoping to provide new insight for the mechanism research of CLCN5 and the specific treatment of Dent disease type 1.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective To investigate the influencing factors of Mismatch ratio in computed tomography perfusion(CTP)and dif-fusion weighted imaging(DWI)to assess the lesion outcome after treatment in patients with acute ischemic stroke(AIS).Methods Whether there were any differences in clinical and imaging data of AIS patients were analyzed retrospectively between the Mismatch ratio＞1.2 group and the Mismatch ratio≤1.2 group,and between the hemorrhagic transformation group and the non-hemorrhagic transformation group.Results The age of onset and National Institutes of Health Stroke Scale(NIHSS)score of AIS patients in the group with Mismatch ratio＞1.2 were greater than those in the group with Mismatch ratio≤1.2.The Mismatch ratio＞1.2 group had lower incidence of hyperlipidemia,new infarct foci,and higher hypercoagulability,cerebral hemorrhage,as well as large cerebral infarction.The NIHSS score was higher in the hemorrhagic transformation group than the non-hemorrhagic transformation group,and the incidence of large cerebral infarction and digital subtraction angiography(DSA)thrombectomy was higher in the former than in the latter.Multifactorial logistic analysis showed that age,NIHSS score,and hyperlipidemia were independent risk factors for AIS patients with Mismatch ratio＞1.2 and large cerebral infarction was an independent risk factor for hemorrhagic transformation.Conclusion The Mismatch ratio in CTP is correlated with age,NIHSS score,and hyperlipidemia in patients with AIS and large cerebral infarction is correlated with hemorrhagic transformation.

Objective　To provide a data foundation not only for food safety supervision and pollution source tracing, but also for the clinical treatment of drug-resistant bacteria in barreled drinking water, the drug resistance and type Ⅲ secretion system (T3SS) virulence genes carriage of Pseudomonas aeruginosa detected in barreled drinking water in Hainan Province were investigated, and the correlative relationship between strain ribosomal subtypes and virulence genes were then discussed. Methods The drug resistance of the isolated 55 strains of Pseudomonas aeruginosa was confirmed by using VITEK 2 Compact automatic microbial drug sensitivity system, and the T3SS virulence genes ExoU, ExoS, ExoT and ExoY were amplified by PCR, bacterial strain subtypes and homology were analyzed by the RiboPrinter automatic microbial gene fingerprint identification system. Results The drug sensitivity results showed that Pseudomonas aeruginosa isolated from barreled water had relatively low drug resistance, though one strain of multidrug-resistant Pseudomonas aeruginosa was discovered, resistant to imipenem, ciprofloxacin and cefepime. The distribution of T3SS virulence genes showed four genotypic combinations: ExoT+/ExoY+/ExoS+/ExoU- (45.45%, 25/55), ExoT+/ExoY+/ExoS-/ExoU+ (34.55%, 19/55), ExoT+/ExoY-/ExoS-/ExoU+(18.18%, 10/55), ExoT+/ExoY+/ExoS+/ExoU+ (1.82%, 1/55). Ribosomal typing results showed that the Pseudomonas aeruginosa strains were divided into six subtypes, the numbers of each subtype accounted for 24 (43.64%), 1 (1.82%), 25 (45.45%), 1 (1.82%), 3 (5.45%) and 1 (1.82%) respectively, with subtype Ⅰ and subtype Ⅲ being dominant. The main T3SS genotypes of the top two subtype I and subtype III were ExoT+/ExoY+/ExoS-/ExoU+ (16/24, 66.67%) and ExoT+/ExoY+/ExoS+/ExoU- (22/25, 88%). Conclusions The T3SS secretion system exhibits the characteristics of multiple virulence genes' coordinated expression, and there is a certain correlation between subtypes of bacterial strains and virulence genotypesThe exploration of the relationship between them provides guidance for tracing the source of Pseudomonas aeruginosa contamination, production control, clinical treatment in barrelled drinking water, and preliminarily establishes the initial data of local Pseudomonas aeruginosa strains in barrelled drinking water as well the related drug sensitivity data in Hainan.

Objective: To investigate the clinical effect of percutaneous transhepatic bile duct drainage guided by ultrasound. Methods: From June 2016 to June 2018, 100 patients with obstructive jaundice in Lishui Central Hospital were treated with ultrasound-guided percutaneous transhepatic bile duct drainage.The success rate and postoperative complications of the patients were analyzed. Results: Among 100 cases, 98 cases were successful, 2 cases failed, and the failure rate was 2%.The success rate of one-time catheterization in 0.5-2.0 cm patients with intrahepatic bile duct diameter(98.91%) was significantly higher than that in intrahepatic bile duct diameter 0.3-0.4 cm patients(87.50%), compared with two different diameter puncture catheterization, the difference was statistically significant(χ²=12.369, P<0.05). All 98 cases with successful puncture were followed up after operation (P<0.05), and there was no statistically significant difference between the two groups(P<0.05). The drainage tube was removed in 2 cases, bile duct infection was found in 2 cases, the remaining patients were unobstructed, and there were no obvious complications. Conclusion Ultrasound-guided percutaneous transhepatic catheterization and drainage for the treatment of obstructive jaundice caused by malignant tumor is simple, reliable, safe and effective, and has a certain clinical value.It is worthy of popularizing and application.

Objective To evaluate the value of ultrasound elastography combined with serum markers in the assessment of chronic hepatitis B fibrosis. Methods 100 patients with chronic hepatitis B liver fibrosis who were diagnosed and treated in our hospital from January 2015 to December 2017 were randomly selected. All patients were given hepatic histopathological tests, serological tests, and ultrasound elastography. The liver biopsy results were taken as the final diagnosis results. The accuracy of classification of hepatitis B fibrosis by the combined diagnosis of ultrasound elastography and serum markers was observed. Results The total accuracy of the combined examination was 91.00％ with histological examination as the final results. There was no statistically significant difference between the results of the two examinations (P>0.05). The ultrasound elastography score and FIB4 score in the patients with hepatitis B fibrosis grade F1-F4 were increased along with the increase of grade, and there was statistically significant difference (P<0.05). Conclusion Ultrasound elastography combined with serum markers has an important clinical value in the assessment of the degree of chronic hepatitis B fibrosis. It is non-invasive, easy to operate and highly accurate, and can provide a reliable basis for disease diagnosis and staging.

Objective To compare the diagnostic value of ultrasound,molybdenum target,magnetic resonance(MRI)and single examination for breast cancer.Methods From January 2017 to February 2018,100 patients with suspected breast cancer in Lishui Central Hospital were selected in the study.All patients were detected by ultrasound,mammography and MRI three ways for diagnosis.The results were verified with postoperative pathologic results as the standard.The diagnosis accuracy of three ways for breast cancer were analyzed.Results The detection accuracy of three ways joint detection in patients with breast cancer was the highest(91.00％),which was significantly higher than that of ultrasound(63.00％),mammography(72.00％)and MRI(72.00％)in single mode,the differences were statistically significant(χ2 =22.364,20.154,16.032,all P<0.05).Conclusion Ultrasonography,molybdenum target X ray and MRI have their respective advantages in the process of breast cancer differentiation and diagnosis,and the detection rate can be significantly improved if combined use.