A ligamentum teres hepatis and falciform ligament 'belt and braces' approach in laparoscopic pancreaticoduodenectomy using a modified Blumgart anastomosis to minimize severe pancreatic fistula and post-operative complications.

BACKGROUND: To determine whether ligamentum teres hepatis and falciform ligament, wrapped around the gastroduodenal artery (GDA) and reinforced the posterior wall in pancreatojejunostomy (PJ), protects the GDA stump and other skeletal blood vessels from erosive hemorrhage and reduces the incidence of clinically relevant post-operative pancreatic fistula (CR-POPF) and post-operative complications after laparoscopic pancreaticoduodenectomy (LPD). METHODS: We reviewed patients undergone LPD between January 2019 and June 2023. Patients were divided into two groups according to whether the ligamentous flap had been used to wrap the GDA stump (Group A) or to reinforce the posterior wall in PJ, together with the GDA wrapping procedure (Group B). Peri-operative data were reviewed to determine the effectiveness of this approach in preventing CR-POPF, post-pancreatectomy hemorrhage (PPH), and other complications. RESULTS: We enrolled 272 patients (Group A, 154 patients; Group B, 118 patients). Group B patients had significantly fewer ≥ Grade II Clavien-Dindo classification morbidities and CR-POPFs (P < 0.05), and lower length of hospital stay (LOS) and abdominal drainage tube insertion times. Risk factor analysis indicated that main pancreatic duct dilation, the PJ reinforcement procedure, and soft pancreatic tissue were associated with ≥Grade II Clavien-Dindo morbidities and CR-POPF complications. CONCLUSIONS: The ligamentous flap application in LPD provided shelter to GDA stump and other skeletal blood vessels under PJ from erosive digestive juices, reinforced the posterior wall in PJ, reduced the incidence of CR-POPF and ≥Grade II Clavien-Dindo classification morbidities. This simple procedure is effective for improving surgical safety of LPD.

Unraveling the Spectrum of Ocular Toxicity with Oxaliplatin: Clinical Feature Analysis of Cases and Pharmacovigilance Assessment of the US Food and Drug Administration Adverse Event Reporting System Database.

PURPOSE: Ocular adverse events (oAEs) are a class of adverse events associated with oxaliplatin that are realistically observed in real-world settings. Herein, we aim to describe the clinical characteristics of oAEs associated with oxaliplatin through a systematic review of case reports and to assess a potential safety signal. METHODS: PubMed, Embase, and Cochrane Library databases were used to retrieve case reports. The global disproportionality study was performed leveraging the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2023. Bayesian information component (IC) and reporting odds ratio (ROR) were applied to identify and evaluate potential oAEs associated oxaliplatin. FINDINGS: A total of 20 cases from the systematic case review (of 13 screened articles) were reported on oAEs associated with oxaliplatin, with ages between 26 and 76 years. Therein, 16 (84.2%) cases described loss of vision, and the remaining cases presented with bilateral blepharoptosis, papilledema, and optic disc swelling. Insights from the US Food and Drug Administration Adverse Event Reporting System database showed that oAEs accounted for 4.28% (n = 1194) of the overall oxaliplatin-related adverse event reports, of which 1140 (95.48%) had a serious outcome. The median (interquartile range) onset time of oAEs with oxaliplatin was day 1 (0-25; n = 649). Disproportionality analysis revealed that ocular injuries NEC (n = 28, ROR, 22.72; lower limit of the 95% 2-sided CI for IC, 3.12) was the most significant signals detected. Additionally, unexpected significant oAEs, including eyelid ptosis, eyelid edema, eye movement disorder, blepharospasm, periorbital edema, swelling of eyelid, ophthalmoplegia, retinal vein thrombosis, cataract nuclear, blindness cortical, cataract subcapsular, and lacrimation disorder, were also reported disproportionality. IMPLICATIONS: Our study systematically described the characteristics and outcomes of oxaliplatin-related ocular toxicity and also uncovered potential oAEs that were not disclosed in the package insert. Further prospective epidemiologic studies to validate these findings are warranted.

Transcriptomic Differences by RNA Sequencing for Evaluation of New Method for Long-Time In Vitro Culture of Cryopreserved Testicular Tissue for Oncologic Patients.

BACKGROUND: Earlier studies have established that culturing human ovarian tissue in a 3D system with a small amount of soluble Matrigel (a basement membrane protein) for 7 days in vitro increased gene fusion and alternative splicing events, cellular functions, and potentially impacted gene expression. However, this method was not suitable for in vitro culture of human testicular tissue. OBJECTIVE: To test a new method for long-time in vitro culture of testicular fragments, thawed with two different regimes, with evaluation of transcriptomic differences by RNA sequencing. METHODS: Testicular tissue samples were collected, cryopreserved (frozen and thawed), and evaluated immediately after thawing and following one week of in vitro culture. Before in vitro culture, tissue fragments were encapsulated in fibrin. Four experimental groups were formed. Group 1: tissue quickly thawed (in boiling water at 100 °C) and immediately evaluated. Group 2: tissue quickly thawed (in boiling water at 100 °C) and evaluated after one week of in vitro culture. Group 3: tissue slowly thawed (by a physiological temperature 37 °C) and immediately evaluated. Group 4: tissue slowly thawed (by a physiological temperature 37 °C) and evaluated after one week of in vitro culture. RESULTS: There are the fewest differentially expressed genes in the comparison between Group 2 and Group 4. In this comparison, significantly up-regulated genes included C4B_2, LOC107987373, and GJA4, while significantly down-regulated genes included SULT1A4, FBLN2, and CCN2. Differential genes in cells of Group 2 were mainly enriched in KEGG: regulation of actin cytoskeleton, lysosome, proteoglycans in cancer, TGF-beta signaling pathway, focal adhesion, and endocytosis. These Group 2- genes were mainly enriched in GO: spermatogenesis, cilium movement, collagen fibril organization, cell differentiation, meiotic cell cycle, and flagellated spermatozoa motility. CONCLUSIONS: Encapsulation of testicular tissue in fibrin and long-time in vitro culture with constant stirring in a large volume of culture medium can reduce the impact of thawing methods on cryopreserved testicular tissue.

Laparoscopic Duodenum and Spleen-Preserving Subtotal or Total Pancreatectomy: A Parenchyma-Sparing Strategy for Main Duct Intraductal Papillary Mucinous Neoplasms (with Video).

BACKGROUND: For premalignant main duct intraductal papillary mucinous neoplasms (MD-IPMN), laparoscopic duodenum and spleen-preserving subtotal or total pancreatectomy (LDSP-STP/TP) seems to be a viable option for parenchyma-sparing pancreatectomy. PATIENTS AND METHODS: On the basis of the imaging features, family history, genomic alterations, intraoperative ultrasound examination, and frozen section evaluation, we have proposed patient selection strategies for the LDSP-STP/TP technique for the first time. Additionally, a comprehensive step-by-step overview of this technique has been provided. To date, we have performed five LDSP-STP procedures and one LDSP-TP procedure. RESULTS: We successfully performed selective resection of the affected pancreatic parenchyma while preserving the duodenum, common bile duct (CBD), spleen, and splenic artery and vein. The operation time ranged from 295 to 495 min, with blood loss ranging from 100 to 300 mL. Postoperative pathological results revealed low-grade dysplasia in the resected pancreatic samples and margins. The patients resumed eating within 3-5 days after surgery, and all postoperative complications were classified as grade I according to the Clavien-Dindo classification. At the 3-month follow-up, there were no cases of CBD ischemic stenosis, splenic ischemia, or pseudocyst formation observed. For patients who received LDSP-STP, the longitudinal diameter of the remaining pancreatic tail ranged from 2.2 to 4.6 cm, and they demonstrated satisfactory long-term blood glycemic control. CONCLUSIONS: LDSP-STP/TP demonstrates technical feasibility and safety. It allows for the selective resection of the affected pancreatic parenchyma, thereby minimizing the impact of pancreatic functional impairment. However, it is crucial to validate this technique through long-term prospective observations.

New Insights into the Mechanism by Which the Pituitary Gland Copes with Hypoxia Stress Based on a Transcriptomic Analysis of Megalobrama amblycephala.

Hypoxia is a common environmental stressor in aquatic ecosystems, and during the cultivation process, Megalobrama amblycephala is prone to death because it is hypoxia-intolerant, which brings huge economic losses to farmers. The pituitary gland is a crucial endocrine gland in fish, and it is mainly involved in the secretion, storage, and regulation of hormones. In the present study, we compared the transcriptional responses to serious hypoxia in the pituitary gland among hypoxia-sensitive (HS) and hypoxia-tolerant (HT) M. amblycephala and a control group that received a normal oxygen supply (C0). The fish were categorized according to the time required to lose balance during a hypoxia treatment. A total of 129,251,170 raw reads were obtained. After raw sequence filtering, 43,461,745, 42,609,567, and 42,730,282 clean reads were obtained for the HS, HT, and C0 groups, respectively. A transcriptomic comparison revealed 1234 genes that were differentially expressed in C0 vs. HS, while 1646 differentially expressed genes were obtained for C0 vs. HT. In addition, the results for HS vs. HT showed that 367 upregulated and 41 downregulated differentially expressed genes were obtained for a total of 408 differentially expressed genes. A KEGG analysis of C0 vs. HS, C0 vs. HT, and HS vs. HT identified 315, 322, and 219 enriched pathways, respectively. Similar hypoxia-induced transcription patterns suggested that the downregulated DEGs and enriched pathways were related to pathways of neurodegeneration in multiple diseases, pathways in cancer, thermogenesis, microRNAs in cancer, diabetic cardiomyopathy, and renin secretion. However, in the upregulated DEGs, the PI3K-Akt signaling pathway (C0 vs. HS), microRNAs in cancer (C0 vs. HT), and HIF-1 signaling pathway (HS vs. HT) were significantly enriched. There is a lack of clarity regarding the role of the pituitary gland in hypoxic stress. These results not only provide new insights into the mechanism by which pituitary tissue copes with hypoxia stress in M. amblycephala but also offer a basis for breeding M. amblycephala with hypoxia-resistant traits.

The U-shaped association between age at diagnosis and recurrence in patients with papillary thyroid carcinoma: A retrospective single-institution cohort study.

PURPOSE: Age is a significant predictor of papillary thyroid carcinoma (PTC). At present, the available evidence shows that age at diagnosis has an important impact on the recurrence of PTC. The objective of our investigation was to examine the relationship between age at diagnosis and recurrence in patients with PTC. METHODS: The medical records of patients with PTC who were treated between January 2010 and December 2018 at a single institute in a cancer referral center in China were retrospectively reviewed. The hazard ratios (HRs) and 95 % confidence intervals (CIs) for recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) were assessed using Cox proportional hazard models and restricted cubic splines (RCSs). RESULTS: A total of 13758 patients were included in the study. With a median follow-up of 60 months (range 12-277), a total of 687 patients experienced recurrence, and 90 patients died. The 5-year RFS, LRRFS and DMFS rates were 95.0 % (95 % CI 94.6%-95.4 %), 95.8 % (95 % CI 95.4%-96.2 %) and 98.8 % (95 % CI 98.6%-99.0 %), respectively. The adjusted smooth RCS curves revealed a U-shaped association between age at diagnosis and RFS, LRRFS, and DMFS. After adjusting for potential confounding variables, both younger (≤30 years) and older (≥55 years) patients exhibited significantly lower RFS and LRRFS rates than did middle-aged patients (31-54 years). Older patients had significantly lower DMFS rates. CONCLUSIONS: This study confirmed a U-shaped association between age at diagnosis and the risk of both locoregional recurrence and distant metastasis.

Microstructure and Mechanical Properties of As-Cast Al-10Ce-3Mg-xZn Alloys.

The microstructure and mechanical properties of as-cast Al-10Ce-3Mg-xZn (x = 0, 1, 3, 5 wt.%) alloys were systematically investigated, with a focus on the effect of Zn on the Al11Ce3 reinforcing phase in the alloy. The results showed that the Al-10Ce-3Mg alloy consists of α-Al, a Chinese-script Al11Ce3 eutectic phase, and a massive Al11Ce3 primary phase. With the addition of Zn content, most of the Zn atoms are enriched in the Al11Ce3 phase to form the acicular-like Al2CeZn2 phase within the Al11Ce3 phase. Increasing the Zn content can increase the volume fraction of the Al11Ce3 phase. Compared to the alloy without Zn addition, the microhardness and elastic modulus of the Al2CeZn2-reinforced Al11Ce3 phase in the alloy with 5 wt.% Zn increased by 18.9% and 9.0%, respectively. Moreover, the room-temperature mechanical properties of Al-10Ce-3Mg alloys were significantly improved due to the addition of Zn element. The alloy containing 5 wt.% Zn had the best tensile properties with an ultimate tensile strength of 210 MPa and a yield strength of 171MPa, which were 21% and 77% higher than those of the alloy without Zn, respectively. The alloy containing 5 wt.% Zn demonstrated a superior retention ratio of tensile strength at 200-300 °C, indicating that the alloy has excellent heat resistance. The improvement in the mechanical properties is primarily attributed to second-phase strengthening and solid solution strengthening.

PPARγ activation ameliorates PM2.5-induced renal tubular injury by inhibiting ferroptosis and epithelial-mesenchymal transition.

Exposure to fine particulate matter (PM2.5) has been associated with the development and progression of renal disease. Peroxisome proliferator-activated receptor gamma (PPARγ), a key transcription factor involved in inflammation as well as lipid and glucose metabolism, helps maintain the integrity of tubular epithelial cells. However, the precise role of PPARγ in PM2.5-induced tubular injury remains unclear. In this study, we investigated the regulatory effects of PPARγ on PM2.5-induced ferroptotic stress and epithelial-mesenchymal transition (EMT) in tubular (HK-2) cells. We found that downregulation of PPARγ expression was correlated with EMT in PM2.5-exposed cells. Pretreatment with the PPARγ agonist 15d-PGJ2 protected the cells from EMT by reducing ferroptotic stress, whereas that with the PPARγ antagonist GW9662 promoted EMT. Furthermore, pretreatment with ferrostatin-1 (Fer-1) significantly prevented PM2.5-induced EMT and downregulation of PPARγ expression. Notably, overexpression of PPARγ blocked PM2.5-induced downregulation of E-cadherin and GPX4 expression and upregulation of α-SMA expression. This study highlights the complex associations of PPARγ with ferroptosis and EMT in PM2.5-exposed tubular cells. Our findings suggest that PPARγ activation confers protection against PM2.5-induced renal injury.

Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.

Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database.

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Optimizing Silver Paste Conductivity with Controlled Convection for Nanowrinkle Growth.

Conductive silver paste plays a crucial role as an interconnecting material between electrodes and circuits in electronic circuits and solar cells. The quality of the silver paste is greatly influenced by the preparation of the conductive-phase silver powder and the sintering process. This study investigated the impact of fluid dynamics on the preparation of silver powder. Combined with X-ray diffractometer characterization and molecular dynamics simulation, the formation mechanism of wrinkled silver powder was explained. The wrinkled silver powder replaced the traditional smooth spherical silver powder, and the point contact between the smooth silver powder turned into a line and surface contact. After mixing and sintering with the micrometer flake silver powder, the electrical conductivity and sintering morphology of the silver paste were improved. Compared with the silver content of conventional silver paste (≥75 wt %), the silver paste of (9.23 ± 0.68) × 10-6 Ω cm can be prepared by curing at 250 °C for 45 min when wrinkled powder/flake powder = 1:1 and silver paste content was only 66.7%. This research work provides a new idea for the morphology control of submicrometer silver powder, which has important applications in the field of low-temperature silver paste for new N-type batteries.

Evaluating the efficacy of laparoscopic radical antegrade modular pancreatosplenectomy in selected early-stage left-sided pancreatic cancer: a propensity score matching study.

BACKGROUND: Laparoscopic radical pancreatectomy is safe and beneficial for recectable pancreatic cancer, but the extent of resection for early-stage tumors remains controversial. METHODS: Consecutive patients with left-sided pancreatic cancer who underwent either laparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS, n = 54) or laparoscopic distal pancreatosplecnectomy (LDP, n = 131) between October 2020 and December 2022 were reviewed. The preoperative radiological selection criteria were as follows: (1) tumor diameter ≤ 4 cm; (2) located ≥ 1 cm from the celiac trunk; (3) didn't invade the fascial layer behind the pancreas. RESULTS: After 1:1 propensity score matching (LRAMPS, n = 54; LDP, n = 54), baseline data were well-balanced with no differences. LRAMPS resulted in longer operation time (240.5 vs. 219.0 min, P = 0.020) and higher intraoperative bleeding volume (200 vs. 150 mL, P = 0.001) compared to LDP. Although LRAMPS harvested more lymph nodes (16 vs. 13, P = 0.008), there were no statistically significant differences in lymph node positivity rate (35.2% vs. 33.3%), R0 pancreatic transection margin (94.4% vs. 96.3%), and retroperitoneal margin (83.3% vs. 87.0%) rate. Postoperative complications did not significantly differ between the two groups. However, LRAMPS was associated with increased drainage volume (85.0 vs. 40.0 mL, P = 0.001), longer time to recover semi-liquid diet compared to LDP (5 vs. 4 days, P < 0.001) and increased daily bowel movement frequency. Tumor recurrence pattern and recurrence-free survival were comparable between the two groups, but the adjuvant chemotherapy regimens varied, and the completion rate of the 6-month intravenous chemotherapy was lower in the LRAMPS group compared to the LDP group (51.9% vs. 75.9%, P = 0.016). CONCLUSIONS: LRAMPS did not provide oncological benefits over LDP for left-sided pancreatic cancer within the selection criteria, but it increased operation time, intraoperative bleeding, and postoperative bowel movement frequency. These factors impacted the regimen selection and completion of adjuvant chemotherapy, consequently compromising the potential benefits of LRAMPS in achieving better local control.

Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.

Background: While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. Methods: A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2nd line, P=0.04; HR 1.88 for ≥3rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. Conclusions: In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.

Characteristics and outcomes of cancer patients admitted to intensive care units in cancer specialized hospitals in China.

PURPOSE: Standard intensive care unit (ICU) admission policies and treatment strategies for patients with cancer are still lacking. To depict the current status of admission, characteristics, and outcomes of patients with cancer in the ICU. METHODS: A multicenter cross-sectional study was performed from May 10, 2021 to July 10, 2021, in the ICU departments of 37 cancer-specialized hospitals in China. Clinical records of all admitted patients aged ≥ 14 years and ICU duration > 24 h with complete data were included. Demographic information, clinical history, severity score at admission, ICU critical condition diagnosis and treatment, ICU and in-hospital outcomes and 90 days survival were also collected. A total of 1455 patients were admitted and stayed for longer than 24 h. The most common primary cancer diagnoses included lung, colorectal, esophageal, and gastric cancer. RESULTS: Patients with lung cancer were admitted more often because of worsening complications that occurred in the clinical ward. However, other cancer patients may be more likely to be admitted to the ICU because of postoperative care. ICU-admitted patients with lung or esophageal cancer tended to have more ICU complications. Patients with lung cancer had a poor overall survival prognosis, whereas patients with colorectal cancer appeared to benefit the most according to 90 days mortality rates. CONCLUSION: Patients with lung cancer require more ICU care due to critical complications and the overall survival prognosis is poor. Colorectal cancer may benefit more from ICU management. This information may be considered in ICU admission and treatment strategies.

How renal toxins respond to renal function deterioration and oral toxic adsorbent in pH-controlled releasing capsule.

The number of patients with chronic kidney disease (CKD) is increasing. Oral toxin adsorbents may provide some value. Several uremic toxins, including indoxyl sulfate (IS), p-cresol (PCS), acrolein, per- and poly-fluoroalkyl substances (PFAS), and inflammation markers (interleukin 6 [IL-6] and tumor necrosis factor [TNF]-alpha) have been shown to be related to CKD progression. A total of 81 patients taking oral activated charcoal toxin adsorbents (AC-134), which were embedded in capsules that dissolved in the terminal ileum, three times a day for 1 month, were recruited. The renal function, hemoglobulin (Hb), inflammation markers, three PFAS (PFOA, PFOS, and PFNA), and acrolein were quantified. Compared with the baseline, an improved glomerular filtration rate (GFR) and significantly lower acrolein were noted. Furthermore, the CKD stage 4 and 5 group had significantly higher concentrations of IS, PCS, IL-6, and TNF but lower levels of Hb and PFAS compared with the CKD Stage 3 group at baseline and after the intervention. Hb was increased only in the CKD Stage 3 group after the trial (p = .032). Acrolein did not differ between the different CKD stage groups. Patients with improved GFR (responders) (about 77%) and nonresponders had similar baseline GFR. Responders had higher acrolein and PFOA levels throughout the study and a more significant reduction in acrolein, indicating a better digestion function. Both the higher PFOA and lower acrolein may be related to improved eGFR (and possibly to improvements in proteinuria, which we did not measure. Proteinuria is associated with PFAS loss in the urine), AC-134 showed the potential to improve the GFR and decrease acrolein, which might better indicate renal function change. Future studies are needed with longer follow-ups.

Heterogeneity of Multiple Pancreatic Neuroendocrine Tumors Identified by 68Ga-DOTANOC and 68Ga-Exendin-4 PET/CT in a Patient with Endogenous Hyperinsulinemic Hypoglycemia and Multiple Endocrine Neoplasia 1.

INTRODUCTION: Insulinomas are the most frequent functional pancreatic neuroendocrine tumors. In about 10% of cases, insulinomas are associated with hereditary syndromes, including multiple endocrine neoplasia 1 (MEN1). CASE PRESENTATION: Herein, we present a 44-year-old female with recurrent hypoglycemia. In December 1998, this patient underwent resection of two pancreatic lesions due to hypoglycemia and was diagnosed with insulinoma. After the operation, the symptoms of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently, as did coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73 mmol/L and 15.2 U/L (2.6-11.8 U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of the somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT was added to localize the insulinoma. Most lesions with high expression of SSTR in the body and tail of the pancreas manifested parts of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide-1 receptor (GLP-1R) was only detected by 68Ga-exendin-4 PET/CT. It showed inter-tumor heterogeneity in the expression of SSTR and GLP-1R. From the distal pancreatectomy, a total of 5 tumors were found in the body and tail of the pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging findings of dual-tracer PET/CT. CONCLUSION: From this case, a combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients with MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contribute to detect all the NET lesions and locate the tumors with secretion of insulin.

Numerical Simulation and Machine Learning Prediction of the Direct Chill Casting Process of Large-Scale Aluminum Ingots.

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

Proximity labeling-assisted click conjugation for electrochemical analysis of specific subpopulations in circulating extracellular vesicles.

Sensitive and accurate analysis of specific subpopulations in circulating extracellular vesicles (EVs) can provide a wealth of information for cancer diagnosis and management. Thus, we propose herein a new electrochemical biosensing method based on a proximity labeling-assisted click conjugation strategy. The method's core design is use of antibody-guided proximity labeling to equip target EVs with a large amount of alkyne groups, so that azide-tagged silver nanoparticles can be accurately loaded onto target EV surfaces, via click conjugation, to generate significant electrochemical responses. Adopting CD44-positive EVs as the model, the electrochemical method was demonstrated by analyzing target EVs across a wide linear range (103-109 particles/mL) with acceptable sensitivity and specificity. Satisfactory utility in clinical blood samples, and versatility with human epidermal growth factor receptor-2-positive EVs as alternative targets, were also shown. This method may thus provide a novel approach to specific subgroup analyses of circulating EVs, and is expected to offer reliable guidance for cancer diagnoses and management strategies.

Eu3+-Doped Anionic Zinc-Based Organic Framework Ratio Fluorescence Sensing Platform: Supersensitive Visual Identification of Prescription Drugs.

Advanced techniques for both environmental and biological prescription drug monitoring are of ongoing interest. In this work, a fluorescent sensor based on an Eu3+-doped anionic zinc-based metal-organic framework (Eu3+@Zn-MOF) was constructed for rapid visual analysis of the prescription drug molecule demecycline (DEM), achieving both high sensitivity and selectivity. The ligand 2-amino-[1,1'-biphenyl]-4,4'-dicarboxylic acid (bpdc-NH2) not only provides stable cyan fluorescence (467 nm) for the framework through intramolecular charge transfer of bpdc-NH2 infinitesimal disturbanced by Zn2+ but also chelates Eu3+, resulting in red (617 nm) fluorescence. Through the synergy of photoinduced electron transfer and the antenna effect, a bidirectional response to DEM is achieved, enabling concentration quantification. The Eu3+@Zn-MOF platform exhibits a wide linear range (0.25-2.5 µM) to DEM and a detection limit (LOD) of 10.9 nM. Further, we integrated the DEM sensing platform into a paper-based system and utilized a smartphone for the visual detection of DEM in water samples and milk products, demonstrating the potential for large-scale, low-cost utilization of the technology.