Case report: Translational treatment of unresectable intrahepatic cholangiocarcinoma: Tislelizumab, Lenvatinib, and GEMOX in one case.

Background: Intrahepatic cholangiocellular carcinoma (ICC) is one of the most common invasive malignancies. Currently, ICC is treated with radical surgical resection. However, the majority of patients are diagnosed at an advanced stage, making surgery ineligible for them. Case presentation: We present a case of advanced ICC, which could not undergo radical surgery due to tumor invasion of liver blood vessels. The gemcitabine and oxaliplatin (GEMOX) regimen combined with Tislelizumab immunotherapy and Lenvatinib targeted therapy for 8 cycles resulted in significant tumor shrinkage significantly and the vascular invasion disappeared. CA19-9 levels were reduced to normal levels. Partial remission and successful tumor transformation were achieved. The patient underwent a successful radical surgical resection, including cholecystectomy, resection of liver segments IV, V, and VIII, as well as a regional lymphatic dissection procedure, resulting in complete pathological remission. Conclusion: Tumor-free surgical margins (R0) resection of patients with advanced ICC after combination of immune, targeted and chemotherapy is rare, and there are almost no cases of complete postoperative remission. The GEMOX regimen in combination with Tislelizumab and Lenvatinib has a good antitumor efficacy and safety profile, and may be a feasible and safe translational treatment option for advanced ICC.

Analysis of surgical treatment of appendix neuroendocrine neoplasms-17 years of single-center experience.

BACKGROUND/AIM: This study investigated the clinicopathological characteristics and treatment of appendix neuroendocrine neoplasms in appendectomy specimens of our center. MATERIALS AND METHODS: The clinicopathological data, including age, sex, preoperative clinical manifestation, surgical method, and histopathological examination results of 11 patients with appendix neuroendocrine neoplasms confirmed by surgery and pathology between November 2005 and January 2023, were retrospectively analyzed. RESULTS: In the histopathological examination of 7277 appendectomy specimens, 11 cases (0.2%) had appendix neuroendocrine neoplasms. Among the 11 patients, 8(72.7%) were males, and 3(27.3%) were females, with an average age of 48.1 years. All patients underwent emergency surgery. A total of 9 patients underwent open appendectomy, including 1 patient who underwent second-stage simple right hemicolectomy after an appendectomy, and two who underwent laparoscopic appendectomy. All 11 patients were followed up for a period of 1 to 17 years. All patients survived without any indication of tumor recurrence. CONCLUSION: Appendiceal neuroendocrine neoplasms are low-grade malignant tumors originating from neuroendocrine cells. They are rarely seen in clinical practice and are often treated based on acute and chronic appendicitis symptoms. These tumors are challenging to diagnose before surgery due to the lack of specificity in clinical manifestations and auxiliary examinations. The diagnosis generally depends on postoperative pathology and immunohistochemistry. Despite the diagnostic challenges, these tumors have a favorable prognosis.

A rapid and sensitive UPLC-MS/MS method for the determination of zanubrutinib in beagle plasma and its application in pharmacokinetics.

A reliable and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of zanubrutinib in the plasma of beagle dogs. The column used was an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 µm), maintained at 40°C with an injection volume of 2 µl. The gradient elution program was as follows: 0-1 min, 10-10% A; 1-1.1 min, 10-90% A; 1.1-2.1 min, 90-90% A; 2.1-2.2 min, 90-10% A; 2.2-3.0 min, 10-10% A. Mobile phase A was 0.1% formic acid, B was acetonitrile, and the total analysis time was 3 min. The mass spectrometry was performed in positive ion mode, and the scanning mode was multi-reaction monitoring mode with electrospray ionization as the ion source; m/z 472.2 → 455.01 for zanubrutinib and m/z 441.03 → 137.99 for ibrutinib (internal standard). The plasma samples were processed by protein precipitation. The standard curve showed good linearity (r2 = 0.999 8) in the range of 1.0-1,000 ng/ml (zanubrutinib) with a low limit of quantification of 1 ng/ml. Also, the intra-day and inter-day precision (RSD) was <5.88% and the accuracy (RE) ranged from -1.56 to 1.08%; the recoveries of zanubrutinib in beagle plasma ranged from 90.12 to 93.53% (RSD 1.67-6.42%) and the ME values of zanubrutinib were 98.70-101.06% (RSD 5.37-8.49%, n = 6). All values meet US Food and Drug Administration requirements. A rapid, highly selective and sensitive method for the determination of zanubrutinib concentration in plasma by UPLC-MS/MS was successfully developed. This method is suitable for pharmacokinetic studies in beagle dogs by following oral administration of zanubrutinib.

Overexpression of Dermokine-α enhances the proliferation and epithelial-mesenchymal transition of pancreatic tumor cells.

Pancreatic cancer is a prevalent malignancy of the digestive system and a major cause of cancer-associated deaths. Previous studies have shown that mutation in the dermokine-ß (DMKN-ß) gene causes pancreatic and colorectal cancer. The role of the carboxy-terminal domain of DMKN-ß and dermokine-α (DMKN-α) genes in cancer tumorigenesis. Herein, the role of DMKN-α in pancreatic cancer (PC) tumorigenesis and the mechanisms underlying this process were investigated. Differentially expressed genes between PC and matched normal cells were identified through RNA-seq analysis, and the corresponding protein expression levels were verified using Western blot analysis. In vivo tumor formation experiment was also performed in nude mice. We found that the DMKN-α gene was overexpressed in cancerous pancreatic cell lines compared to normal pancreatic cell lines. CCK-8, colony formation, RTCA test, wound healing, as well as transwell test showed that the overexpression of DMKN-α enhanced the proliferation, migration, invasion, and EMT of PC cells. In vivo assays confirmed that DMKN-α promotes tumorigenesis. The findings of this study show that DMKN-α is a potential oncogene for pancreatic cancer.

In situ lattice tuning of quasi-single-crystal surfaces for continuous electrochemical modulation.

The ability to control the atomic-level structure of a solid represents a straightforward strategy for fabricating high-performance catalysts and semiconductor materials. Herein we explore the capability of the mechanically controllable surface strain method in adjusting the surface structure of a gold film. Underpotential deposition measurements provide a quantitative and ultrasensitive approach for monitoring the evolution of surface structures. The electrochemical activities of the quasi-single-crystalline gold films are enhanced productively by controlling the surface tension, resulting in a more positive potential for copper deposition. Our method provides an effective way to tune the atom arrangement of solid surfaces with sub-angstrom precision and to achieve a reduction in power consumption, which has vast applications in electrocatalysis, molecular electronics, and materials science.

Prognostic value of small mother against decapentaplegic expression in human gastric cancer.

Gastric cancer is the fifth most common malignancy in the world with alow 5-year survival rate. To date, no study has investigated the prognostic role of the small mother against decapentaplegic (SMAD) in gastric cancer. The association of SMADs with overall survival (OS) of gastric cancer was analyzed on the online Kaplan-Meier (KM) plotter database. Clinical data such as stage, differentiation, gender, treatment, and Her2 mutation status of gastric cancer patients were analyzed. The (E)-SIS3 was used to inhibit SMAD3 expression in gastric cancer cells, and the effects of SMAD3 on gastric cancer cells were analyzed via real-time cellular analysis (RTCA), flow cytometry, colony formation, and immunofluorescence assay. The results showed that the high expression of three members of SMADs (SMAD1, SMAD2, SMAD4) was correlated with afavorable OS of gastric cancer patients. Meanwhile, SMAD3 expression level indicated highly differentiated cancer. We also observed that surgical treatment was associated with high expression level of SMAD1 and SMAD2. Besides, the effect of Her2 on gastric cancer was not noticeable. Moreover, (E)-SIS3 pharmacological assay revealed that inhibition of expression of SMAD3 suppressed the proliferation and migration ability of gastric cancer cells via inducing apoptosis. Collectively, these results demonstrate that the high expression level of three members of SMADs (SMAD1, SMAD2, and SMAD4) is significantly correlated with favorable OS of gastric cancer patients, which is opposite to SMAD3. Thus, SMADs regulate the differentiation of cancer and can be used to guide treatment decisions.

[HONO Pollution Characteristics and Nighttime Sources During Autumn in Guangzhou, China].

Nitrous acid (HONO) plays an important role in atmospheric photochemistry processes because its photolysis provides an efficient source of hydroxyl (OH) radicals in the troposphere. However, few studies exist on HONO in nocturnal chemistry processes. Using the observation data of HONO and related parameters for a super site at Guangzhou Jinan University in October 2015, the pollution processes and sources of HONO during nighttime were analyzed in this study. The results showed that the average concentration of HONO was 4.32 µg ·m-3 during the nighttime, which was 2.6 times its concentration of 1.67 µg ·m-3 in the daytime. The conversion rate of HONO, CHONO, during the nighttime was 0.0068 h-1, and the average contribution of vehicle emissions to HONO was 15.1%, with a peak of 37.8% at 20:00. The average net HONO generation rate from the reaction of NO and OH radicals during the night was 0.44 µg ·(m3 ·h)-1. Correlation analysis suggested that particles could not be the major HONO source, but that relative humidity (RH; 33%-78%) was a key factor. Relevant calculation indicated that the heterogeneous reaction of deposited NO2 on humid ground surfaces could be the main source of HONO during nighttime.