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Abstract Background The TRIANGLE operation benefits patients with pancreatic cancer; however, the Heidelberg triangle, where the operation occurs, contains vessels that can impact safety, especially in laparoscopic pancreaticoduodenectomy (LPD) with the TRIANGLE operation. This study aimed to identify Heidelberg triangle vessel types and their implications in pancreaticoduodenectomy (PD). Methods Retrospective collection of radiographic data was performed from January 2017 to April 2023. Three-dimensional (3D) CT reconstructions were performed on patients. Vascular types in the Heidelberg triangle were classified based on named vessels crossing its interior. The impact of these types on surgical outcomes and complications in PD with the TRIANGLE operation was assessed. Results Preoperative CT reconstruction was conducted on 184 pancreatic surgery patients. The findings revealed 99 patients (53.8%) with the type I Heidelberg triangle, lacking named vessels crossing the interior. Type II (n = 85, 46.2%), with named vessels crossing the interior, was identified. Among reconstructed patients who underwent PD with the TRIANGLE operation (n = 103), they were categorized as type I (n = 57) or type II (n = 46). The results showed that LPD patients with type II had significantly higher median intraoperative blood loss (300 mL vs. 200 mL, P = 0.030) and mean examined lymph nodes (17.2 ± 7.6 vs. 13.4 ± 5.2, P = 0.019) compared to those with type I. No significant differences were found in operative time or postoperative complications. Conclusion The presence of named vessels crossing the interior of the Heidelberg triangle was associated with increased intraoperative bleeding during LPD combined with the TRIANGLE operation. Therefore, targeted preoperative planning is required before the operation, thus improving the safety of the TRIANGLE operation in minimally invasive surgery.

Various types of minimally invasive pancreatic surgery have been carried out in the last decades with promising outcomes reported by early explorers. Nevertheless, there are still controversies on oncologic outcomes and safety in the use of minimally invasive radical surgery for pancreatic ductal adenocarcinoma (PDAC). This consensus, referring to Chinese expert opinions and worldwide researches, aimed to discuss the related issues on minimally invasive radical surgery for PDAC to ensure the perioperative and oncological outcomes. Quality of evidence and strength of recommendations were evaluated based on the GRADE approach. The 15 recommendations covered 5 topics: oncological outcomes and patient safety of laparoscopic and robotic pancreatoduodenectomy, left-side pancreatectomy for PDAC, learning curve, safety of neoadjuvant therapy, and vascular resection in minimally invasive radical surgery for PDAC. This consensus gives reference and guidance to surgeons on the use of minimally invasive radical surgery for PDAC. Although this consensus is not sufficient to answer all the questions about minimally invasive radical surgery for PDAC, it represents the current consensus on the application of the techniques in the treatment of PDAC on the Chinese mainland.

Patients with metastatic pancreatic cancer have limited treatment options and a dismal prognosis. While RET fusion is rare (0.6%) in pancreatic cancer, the efficacy of RET-targeted treatment in patients with TRIM33-RET fusion has not been previously reported. Herein, we presented a case of a 68-year-old man with pancreatic cancer harboring TRIM33-RET fusion who responded remarkably to pralsetinib despite being intolerant to chemotherapy. To our knowledge, this is the first report on the clinical value of a single TRIM33-RET fusion in pancreatic cancer, which may benefit from the targeted therapy.

We designed a novel strategy to define codon usage bias (CUB) in 6 specific small cohorts of human genes. We calculated codon usage (CU) values in 29 non-disease-causing (NDC) and 31 disease-causing (DC) human genes which are highly expressed in 3 distinct tissues, kidney, muscle, and skin. We applied our strategy to the same selected genes annotated in 15 mammalian species. We obtained CUB hierarchical clusters for each gene cohort which showed tissue-specific and disease-specific CUB fingerprints. We showed that DC genes (especially those expressed in muscle) display a low CUB, well recognizable in codon hierarchical clustering. We defined the extremely biased codons as "zero codons" and found that their number is significantly higher in all DC genes, all tissues, and that this trend is conserved across mammals. Based on this calculation in different gene cohorts, we identified 5 codons which are more differentially used across genes and mammals, underlining that some genes have favorite synonymous codons in use. Since of the muscle genes clear clusters, and, among these, dystrophin gene surprisingly does not show any "zero codon" we adopted a novel approach to study CUB, we called "mapping-on-codons". We positioned 2828 dystrophin missense and nonsense pathogenic variations on their respective codon, highlighting that its frequency and occurrence is not dependent on the CU values. We conclude our strategy consents to identify a hierarchical clustering of CU values in a gene cohort-specific fingerprints, with recognizable trend across mammals. In DC muscle genes also a disease-related fingerprint can be observed, allowing discrimination between DC and NDC genes. We propose that using our strategy which studies CU in specific gene cohorts, as rare disease genes, and tissue specific genes, may provide novel information about the CUB role in human and medical genetics, with implications on synonymous variations interpretation and codon optimization algorithms.

Abstract Zinc finger 644 (Zfp644 in mouse, ZNF644 in human) gene is a transcription factor whose mutation S672G is considered a potential genetic factor of inherited high myopia. ZNF644 interacts with G9a/GLP complex, which functions as a H3K9 methyltransferase to silence transcription. In this study, we generated mouse models to unravel the mechanisms leading to symptoms associated with high myopia. Employing TALEN technology, two mice mutants were generated, either with the disease-carrying mutation (Zfp644 S673G ) or with a truncated form of Zfp644 (Zfp644 Δ8 ). Eye morphology and visual functions were analysed in both mutants, revealing a significant difference in a vitreous chamber depth and lens diameter, however the physiological function of retina was preserved as found under the high-myopia conditions. Our findings prove that ZNF644/Zfp644 is involved in the development of high-myopia, indicating that mutations such as, Zfp644 S673G and Zfp644 Δ8 are causative for changes connected with the disease. The developed models represent a valuable tool to investigate the molecular basis of myopia pathogenesis and its potential treatment.

Objectives. Recently, it has been demonstrated that patients with subtle preexisting cognitive impairment were susceptible to delayed neurocognitive recovery (DNR). This present study investigated whether preoperative alterations in gray matter volume, spontaneous activity, or functional connectivity (FC) were associated with DNR. Methods. This was a nested case-control study of older adults (≥60 years) undergoing noncardiac surgery. All patients received MRI scan at least 1 day prior to surgery. Cognitive function was assessed prior to surgery and at 7-14 days postsurgery. Preoperative gray matter volume, amplitude of low-frequency fluctuation (ALFF), and FC were compared between the DNR patients and non-DNR patients. The independent risk factors associated with DNR were identified using a multivariate logistic regression model. Results. Of the 74 patients who completed assessments, 16/74 (21.6%) had DNR following surgery. There were no differences in gray matter volume between the two groups. However, the DNR patients exhibited higher preoperative ALFF in the bilateral middle cingulate cortex (MCC) and left fusiform gyrus and lower preoperative FC between the bilateral MCC and left calcarine than the non-DNR patients. The multivariate logistic regression analysis showed that higher preoperative spontaneous activity in the bilateral MCC was independently associated with a higher risk of DNR (OR=3.11, 95% CI, 1.30-7.45; P=0.011). A longer education duration (OR=0.57, 95% CI, 0.41-0.81; P=0.001) and higher preoperative FC between the bilateral MCC and left calcarine (OR=0.40, 95% CI, 0.18-0.92; P=0.031) were independently correlated with a lower risk of DNR. Conclusions. Preoperative higher ALFF in the bilateral MCC and lower FC between the bilateral MCC and left calcarine were independently associated with the occurrence of DNR. The present fMRI study identified possible preoperative neuroimaging risk factors for DNR. This trial is registered with Chinese Clinical Trial Registry ChiCTR-DCD-15006096.

Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations.