Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Objective:To investigate the Kub stage classification of clinical renal tuberculosis and provide a reference for disease evaluation and management.Methods:A retrospective analysis was conducted on clinical data from 180 patients diagnosed with renal tuberculosis who were admitted to the First Affiliated Hospital of Dali University between January 2011 and December 2022. The 180 cases included 82 males and 98 females. The average age was (44.56±9.62) years. The tuberculosis lesions of 101 cases were on left kidney, while that of 79 cases were on right kidney. Localized/multiple lesions were observed in 118 cases, whereas extensive destruction was found in 62 cases. Moreover, the ureters were involved in 165 cases, and bladder invasion occurred in 139 cases. For patients undergoing renal preservation treatment, a comprehensive approach was employed, including ureteral stricture stenting and regular replacement of double-J stent, percutaneous nephrostomy, excision of tuberculosis lesions or partial nephrectomy, ureter reconstruction, and sigmoidocystoplasty. In cases requiring nephrectomy, either laparoscopic or open surgical approaches are utilized. Based on the results of patient imaging and endoscopy, staging and classification were performed based on the extent of tuberculosis lesions involving the kidneys (K), ureters (u), and bladder (b). The state for each above organ was divided into four stages: K stage (K 1-4), u stage (u 0-u 3), and b stage (b 0-b 3), which were then combined with the actual disease condition for further categorization. The classifications included local intrarenal type(K 1-2u 0b 0), local renal-ureteral involvement type(K 1-2u 1-2b 0-2), multiple renal-ureteral invasion type(K 3u 1-3b 0-2) and extensive destruction type(K 4u 1-3b 1-3). Further analysis was conducted on kidney preservation and subsequent disease progression among patients with different subtypes. Results:Among the 180 patients, 15 cases of local intrarenal type underwent kidney-preserving treatment. Out of these cases, 6 patients (4 patients in stage K 1u 0b 0 and 2 patients in stage K 2bu 0b 0) achieved clinical cure after receiving a pure durative anti-tuberculosis for two years. Additionally, 4 patients in stage K 2au 0b 0 attained clinical cure following anti-tuberculosis drugs combined with partial nephrectomy after two years of follow-up. Furthermore, 5 patients in stage K 2bu 0b 0 underwent ureteroscopy and D-J stent placement for regular stent replacement. The stents were subsequently removed after two years, and the patients remained clinically stable. Among the 47 cases with localized renal-ureteral involvement type, all initially underwent kidney-preserving treatment. Of these, 5 patients in stage K 1u 1b 0-2 achieved clinical remission, while disease progression necessitated nephrectomy for 3 patients in stage K 2au 1-2b 0-2 and 7 patients in stage K 2bu 1-2b 0-2. The remaining patients maintained stable conditions. Among the 56 cases of multiple renal-ureteral invasion type, stable conditions were observed in 9 out of 24 patients with stage K 3u 1-2b 0-2, while disease progression necessitated nephrectomy in 15 cases. Nephrectomy was performed for all 32 patients with stage K 3u 3b 0-2. In instances of extensive destruction type, nephrectomy was conducted for all 62 cases. The progression rates of the local renal-ureteral involvement type and the multiple renal-ureteral invasion type were 21.28% (10/47) and 48.39% (15/31), and the difference was statistically significant ( P<0.05). The kidney preservation rates of the local renal-ureteral involvement type and multiple renal-ureteral invasion type were 78.72% (37/47) and 16.07% (9/56), and the difference was statistically significant ( P<0.001). Conclusions:The Kub stage classification can provide reference to management and monitoring for renal tuberculosis. The patients in the local intrarenal type and local renal-ureteral involvement type are often treated with anti-tuberculosis plus ureteral stent implantation or partial nephrectomy or ureteral reconstruction. The patients in the multiple renal-ureteral invasion type and extensive destruction type are mostly managed by nephrectomy.

Objective Based on the scoping review framework,we collected cancer-related cognitive impairment(CRCI)assessment tools from home and abroad to provide references for the standardized use of such assessment tools.Methods Chinese and English databases,such as Pubmed,Embase,Web of Science Core Collection database,CNIK,Wanfang database,and VIP database,were systematically searched from the establishment of the database to April 12,2024,to extract the basic information of evaluation tools,and the search results were standardized.Results 31 articles were included,of which 26 were about the development or validation of assessment tools,and 5 were about the localization and application of assessment tools,involving 19 subjective assessment tools and 8 objective assessment tools.Most of the subjective assessment tool reliability and validity tests were internal consistency reliability tests and concurrent validity tests;14 subjective assessment tools were multidimensional scales;6 objective assessment tools measured retest reliability;4 were unidimensional measures.Conclusion The assessment tools chosen for the current studies vary.It is recommended to choose the evaluation tools and judgment standards recommended by the International Cognitive and Cancer Working Group to carry out relevant research.In the future,the existing CRCI assessment tools should be further verified and improved,and a localized CRCI assessment tool should be continuously introduced or developed.

Objective Based on the scoping review framework,we collected cancer-related cognitive impairment(CRCI)assessment tools from home and abroad to provide references for the standardized use of such assessment tools.Methods Chinese and English databases,such as Pubmed,Embase,Web of Science Core Collection database,CNIK,Wanfang database,and VIP database,were systematically searched from the establishment of the database to April 12,2024,to extract the basic information of evaluation tools,and the search results were standardized.Results 31 articles were included,of which 26 were about the development or validation of assessment tools,and 5 were about the localization and application of assessment tools,involving 19 subjective assessment tools and 8 objective assessment tools.Most of the subjective assessment tool reliability and validity tests were internal consistency reliability tests and concurrent validity tests;14 subjective assessment tools were multidimensional scales;6 objective assessment tools measured retest reliability;4 were unidimensional measures.Conclusion The assessment tools chosen for the current studies vary.It is recommended to choose the evaluation tools and judgment standards recommended by the International Cognitive and Cancer Working Group to carry out relevant research.In the future,the existing CRCI assessment tools should be further verified and improved,and a localized CRCI assessment tool should be continuously introduced or developed.

Objective:To investigate the correlation between morphology of esophageal and gastric mucosal and Helicobacter pylori ( HP) infection under white light gastroscope. Methods:A retrospective analysis was performed on data of 1 339 patients who underwent 13C-urea breath test and white light gastroscopy at the same time in the Southwest Hospital of Army Medical University from September 2018 to August 2019. Chi-square test or Fisher exact probability method was used to analyze the difference on detection rates of 22 indexes of gastroscopic mucosal manifestation between the HP infection group ( n=422) and the non-infection group ( n=917). Then the indexes with difference were further analyzed by binary logistic regression. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve and the sensitivity, specificity, positive predictive value and negative predictive value of prediction of HP infection was calculated. Results:The diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, digestive tract ulcer, nodularity, hyperplastic polyp, xanthoma, atrophy, intestinal metaplasia, and depressive erosion were more common in patients with HP infection (all P<0.05). Binary logistic regression analysis showed that diffuse redness ( P<0.001, OR=75.974, 95% CI: 32.551-177.327), spotted redness ( P=0.002, OR=3.360, 95% CI: 1.536-7.349), mucosal swelling ( P<0.001, OR=3.150, 95% CI: 1.654-5.996) were independent risk factors for HP infection. ROC curve analysis showed that the area under ROC curve of diffuse redness, spotted redness, mucosal swelling, enlarged folds, sticky mucus, peptic ulcer, and depressive erosion predicting HP infection were all greater than 0.5 ( P<0.05), among which, the area under curve of diffuse redness, spotted redness and mucosal swelling predicting HP infection were greater than 0.7. The sensitivities corresponding to the three indicators were 0.735, 0.512, and 0.445, the specificities were 0.992, 0.983, and 0.971, the positive predictive values were 0.978, 0.931, and 0.874, and the negative predictive values were 0.890, 0.814, and 0.792, respectively. Conclusion:Morphological manifestations of esophageal and gastric mucosa, especially diffuse redness, spotted redness, and mucosal swelling, are excellent indicators for HP infection under white light gastroscopy.

Objective To observe the ultrasonographic and pathological features of metaplastic carcinoma with squamous cell component (MCSC) of the breast.Methods The ultrasonographic and pathological features of 7 patients with breast MCSC confirmed pathologically were retrospectively analyzed.Results Seven cases were single lesion and the maximal diameters of the lesions were 2.6-5.1 cm.On two-dimensional imaging,6 lesions with cystic and solid were complex echogenic,only 1 lesion was hypoechoic.All the lesions had irregular shape (lobulated)and indistinct margin.On CDFI imaging,most of lesions had rich blood flow signals with high resistance (resistance index 0.75-0.91),4 lesions were grade l,2 lesions were grade Ⅱ and 1 lesion was grade Ⅰ blood flow signals.On gross histopathological examination,6 masses had cystic cavity,only 1 mass was pure solid.On microscopic histopathological examination,5 masses were adenosqua mous carcinoma,only 2 masses were pure squamous cell carcinoma.Estrogen receptors,progesterone receptors and human epidermal growth factor receptor were negative in 4 masses (triple-negative breast cancer).Conclusion MCSC have some distinguished ultrasonic characteristics of larger volume,cystic-solid mixed echo,posterior echo enhancement,abundant vascularity with high resistance.

Objective To investigate the curative effect and safety of microinvasive percutaneous nephrolithotomy (MPCNL) and ureteroscope lithotripsy (URSL) in treatment of children′s (≤6 years old) middle and upper segment ureteral calculi. Methods Eighty children (≤6 years old) with middle and upper segment ureteral calculi were selected, and they were divided into observation group and control group according to random number table method with 40 cases each. The children of observation group were treated with MPCNL, and the children of control group were treated with URSL. The operation time, hospitalization time, calculi clearance rate of the first phase, decline situation of the postoperative hemoglobin and hematocrit and complication were compared between 2 groups. Results The operation time and hospitalization time in observation group were significantly shorter than those in control group:(45.43 ± 9.76) min vs. (68.32 ± 11.28) min and (8.12 ± 1.03) d vs. (13.45 ± 2.34) d, the calculi clearance rate of the first phase was significantly higher than that in control group: 100.0% (40/40) vs. 62.5%(25/40), the incidence of complication was significantly lower than that in control group:20.0%(8/40) vs. 60.0% (24/40), and there were statistical differences (P<0.05). There were no statistical differences in the decline situation of the postoperative hemoglobin and hematocrit between 2 groups (P>0.05). Conclusions The MPCNL in treatment of children′s middle and upper segment ureteral calculi has short operation time, high calculi clearance rate of the first phase, and low incidence of perioperative complication. Compared with URSL, the URSL is safe and efficient, and it is worthy of clinical application.

Objective To investigate the relationship between acute biliary pancreatitis and pancreaticobiliary maljunction and the role of magnetic resonance cholangiopancreatography(MRCP) in evaluation of pancreatico biliary maljunction.Methods To compare the liver function indicators of different groups of acute biliary pancreatitis patients(153 cases) associated with pancreatico biliary maljunction and without pancreatico biliary maljunction before and after the conservative treatment.Results The 32 acute biliary pancreatitis patients with pancreatico biliary maljunction detected by MRCP were compared with the 121 cases without pancreatico biliary maljunction.The ALT,AST,GGT after conservative treatment in both group of pancreatico biliary maljunction and Npancreatico biliary maljunction were significantly decreased (P ＜ 0.05).ALT,AST and GGT of pancreatico biliary maljunction group were higher than that of Npancreatico biliary maljunction group with statistical significance (P ＜ 0.05).Conclusions MRCP as a noninvasive cholangiopancreatography study of pancreatico biliary maljunction is a safe and reliable examination method,pancreatico biliary maljunction is one of the important causes of acute biliary pancreatitis.

Objective To explore the clinical factors on the functional recovery of spinal cord cavernous hemangioma operation. Methods Fifty cases patients with complete spinal cord cavernous hemangioma were retrospectively analyzed their clinical data and its influence on prognosis of 2 years. Single factor and multiple factors analysis were performed. Results Compared with the preoperative stage,the grade of Aminoff-Logue score of 28 cases(50. 9%)had improved at least one grade,14 cases(25. 5%)patients with no significant changes and 13 cases(23. 6%)with decreased one grade at least. Logistic regression model showed that patients with clinical types(OR=3. 27,95%CI 2. 34-15. 83,P=0. 006),the time of the attacks to the surgery(OR=2. 93,95%CI 1. 41-10. 61,P=0. 012),and the attacks to the operation time( OR=4. 31,95%CI 2. 46 -12. 32,P = 0. 019 ) were related to neurological function recovery of spinal cord cavernous hemangiomas. Conclusion For patients with SCH dysfunction,regardless of what kind of clinical types of neurological dysfunction extent,should receive surgical treatment to improve neurological function recovery rate as soon as possible.

Recent meta-analysis based on both clinical trials and epidemiological studies has revealed the relationship of dietary cholesterol,blood cholesterol level and cholesterol lowering drugs (statins) with colorectal cancer.This review summarises the advances in current evidences of linking cholesterol metabolism and risk of colorectal cancer and the underlying molecular mechanisms based on pharmacogenetics and molecular pathology.