FLT3-selective PROTAC: Enhanced safety and increased synergy with Venetoclax in FLT3-ITD mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability. Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. Through screening and structural optimization, the optimal lead compound PROTAC Z29 showed better specificity than Gilteritinib. Z29 induced FLT3 degradation through the proteasome pathway and inhibited tumor growth in subcutaneous xenograft mice. We verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model compared to Gilteritinib. The combination of Z29 and Venetoclax showed better anti-tumor effects, lower platelet toxicity, and lower hepatic toxicity in FLT3-ITD+ models. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.

Case report and literature analysis: pancreatic hepatoid carcinoma with multiple lymph node metastases progressing to liver metastasis after pancreaticoduodenectomy.

Hepatoid carcinoma is an extrahepatic primary tumor displaying characteristics reminiscent of hepatocellular carcinoma differentiation, which is found in various organs, such as the stomach, ovaries, gallbladder, and pancreas. Reports of pancreatic hepatoid carcinoma remain scarce. Consequently, understanding of this disease remains a priority, with no established consensus on its diagnosis and management. Here, we reported the case of a 45-year-old woman diagnosed with hepatoid carcinoma located in the pancreatic head, accompanied by multiple lymph node metastases. Following pancreaticoduodenectomy, the patient developed liver metastases within 3 months. Subsequently, she underwent adjuvant therapy consisting of Teysuno and Durvalumab following microwave ablation for the liver metastases. Remarkably, the patient has survived for one year without significant disease progression. This case underscores the potential efficacy of immunotherapy as a promising treatment option for pancreatic hepatoid carcinoma. Further research and clinical trials are warranted to explore the optimal management strategies for this rare and challenging malignancy.

CDK5RAP3 is a novel super-enhancer-driven gene activated by master TFs and regulates ER-Phagy in neuroblastoma.

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.

Eco-friendly preparation and characterization of high-performance electrothermal graphene-AgNPs/lignocellulose composites.

Graphene-based (Gr-based) electrothermal heaters, due to their light weight, low electrical resistance, high thermal conductivity, and easy accessibility, have attracted widespread attention in the field of electrothermal heating. To achieve a high steady-state temperature in electrothermal heaters under low voltage, here we constructed a Gr-based film with low electrical resistance. Firstly, we employed non-toxic vitamin C to reduce silver nitrate for the in situ chemical deposition of silver nanoparticles (AgNPs) on the Gr surface. The SEM results confirmed that the AgNPs were uniformly deposited on the Gr surface. The synergistic interaction between AgNPs and Gr provided high-speed electrons transport paths for the film. On the other hand, we employed biodegradable lignocellulose fiber (LCF) as a dispersant and film-forming agent. The aromatic ring structure of LCF interacts with Gr via π-π interactions, aiding the dispersion of Gr in aqueous solutions. SEM results revealed that LCF permeated through the surfaces and interstices of the two-dimensional Gr sheets, providing mechanical support for the composite film. This approach enables the creation of freestanding Gr-AgNPs/LCF electrothermal composites. The resistivity and electrothermal results demonstrated that the obtained 20 wt% Gr-based composite film possessed low electrical resistance (5.4 Ω sq-1) and exhibited an outstanding saturated temperature of 214 °C under a very low input voltage of 7 V. The preparation method of this Gr-based composite film is simple, easy to operate, and environmentally friendly, providing a new reference for the preparation of eco-friendly and high-performance resistance heating electronics.

Establishment of the First National Standard for Neutralizing Antibodies against SARS-CoV-2 XBB Variants.

Neutralizing antibodies (NtAbs) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are indicators of vaccine efficacy that enable immunity surveillance. However, the rapid mutation of SARS-CoV-2 variants prevents the timely establishment of standards required for effective XBB vaccine evaluation. Therefore, we prepared four candidate standards (No. 11, No. 44, No. 22, and No. 33) using plasma, purified immunoglobulin, and a broad-spectrum neutralizing monoclonal antibody. Collaborative calibration was conducted across nine Chinese laboratories using neutralization methods against 11 strains containing the XBB and BA.2.86 sublineages. This study demonstrated the reduced neutralization potency of the first International Standard antibodies to SARS-CoV-2 variants of concern against XBB variants. No. 44 displayed broad-spectrum neutralizing activity against XBB sublineages, effectively reduced interlaboratory variability for nearly all XBB variants, and effectively minimized the geometric mean titer (GMT) difference between the live and pseudotyped virus. No. 22 showed a broader spectrum and higher neutralizing activity against all strains but failed to reduce interlaboratory variability. Thus, No. 44 was approved as a National Standard for NtAbs against XBB variants, providing a unified NtAb measurement standard for XBB variants for the first time. Moreover, No. 22 was approved as a national reference reagent for NtAbs against SARS-CoV-2, offering a broad-spectrum activity reference for current and potentially emerging variants.

Modulation of atherosclerosis-related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives.

Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-E2-related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator-activated receptor (PPAR), nucleotide oligo-structural domain-like receptor thermoprotein structural domain-associated protein 3 (NLRP3), silencing information regulator 2-associated enzyme 1 (Sirt1), nuclear transcription factor-κB (NF-κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor-ß (TGF-ß), and Janus kinase-signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high-intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.

Therapeutic potential of salidroside in preserving rat cochlea organ of corti from gentamicin-induced injury through modulation of NRF2 signaling and GSK3ß/NF-κB pathway.

Salidroside (SAL) is a phenol glycoside compound found in plants of the Rhodiola genus which has natural antioxidant and free radical scavenging properties. SAL are able to protect against manganese-induced ototoxicity. However, the molecular mechanism by which SAL reduces levels of reactive oxygen species (ROS) is unclear. Here, we established an in vitro gentamicin (GM) ototoxicity model to observe the protective effect of SAL on GM-induced hair cells (HC) damage. Cochlear explants of postnatal day 4 rats were obtained and randomly divided into six groups: two model groups (treatment with 0.2 mM or 0.4 mM GM for 24 h); two 400 µmol/L SAL-pretreated groups pretreatment with SAL for 3 h followed by GM treatment (0.2 mM or 0.4 mM) for 24 h; 400 µmol/L SAL group (treatment with SAL for 24 h); control group (normal cultured cochlear explants). The protective effects of SAL on GM-induced HC damage, and on mRNA and protein levels of antioxidant enzymes were observed. HC loss occurred after 24 h of GM treatment. Pretreatment with SAL significantly reduced GM-induced OHC loss. In cochlear tissues, mRNA and protein levels of NRF2 and HO-1 were enhanced in the GM alone group compared with the SAL pretreatment GM treatment group. SAL may protect against GM-induced ototoxicity by regulating the antioxidant defense system of cochlear tissues; SAL can activate NRF2/HO-1 signaling, inhibit NF-κB activation, activate AKT, and increase inhibitory phosphorylation of GSK3ß to decrease GSK3 activity, all of which exert antioxidant effects.

Optimizing robotic thyroid surgery: lessons learned from an retrospective analysis of 104 cases.

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.

Therapeutic Role of Chinese Medicine Targeting Nrf2/HO-1 Signaling Pathway in Myocardial Ischemia/Reperfusion Injury.

Acute myocardial infarction (AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury (MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.

Structural basis for substrate and antibiotic recognition by Helicobacter pylori isoleucyl-tRNA synthetase.

Helicobacter pylori infection is a global health concern, affecting over half of the world's population. Acquiring structural information on pharmacological targets is crucial to facilitate inhibitor design. Here, we have determined the crystal structures of H. pylori isoleucyl-tRNA synthetase (HpIleRS) in apo form as well as in complex with various substrates (Ile, Ile-AMP, Val, and Val-AMP) or an inhibitor (mupirocin). Our results provide valuable insights into substrate specificity, recognition, and the mechanism by which HpIleRS is inhibited by an antibiotic. Moreover, we identified Asp641 as a prospective regulatory site and conducted biochemical analyses to investigate its regulatory mechanism. The detailed structural information acquired from this research holds promise for the development of highly selective and effective inhibitors against H. pylori infection.

The Effect of Group Identity on Chinese College Students' Social Mindfulness: Testing a Moderated Mediation Model.

Purpose: The current study examined the effect of group identity on social mindfulness, how awe mediates this effect, and lastly how empathy may moderate the various indirect pathway. Methods: A total of 2041 Chinese college students were recruited from different universities or colleges to complete the questionnaire including group identity scale, awe scale, empathy scale and social mindfulness scale. This study was conducted using random and convenient sampling, as well as SPSS and its plugin PROCESS as a statistical tool. Results: The present study showed that group identity was positively associated with awe and social mindfulness. Awe was positively associated with social mindfulness. Empathy further moderated the relationship between group identity and awe, awe and social mindfulness, as well as group identity and social mindfulness. Conclusion: The findings of this study shed light on a correlation between group identity and social mindfulness. Furthermore, this study emphasizes the practical importance of intervening in the empathy level of students who have poor empathy in order to increase their social mindfulness.

METTL14/miR-29c-3p axis drives aerobic glycolysis to promote triple-negative breast cancer progression though TRIM9-mediated PKM2 ubiquitination.

The energy metabolic rearrangement of triple-negative breast cancer (TNBC) from oxidative phosphorylation to aerobic glycolysis is a significant biological feature and can promote the malignant progression. However, there is little knowledge about the functional mechanisms of methyltransferase-like protein 14 (METTL14) mediated contributes to TNBC malignant progression. Our study found that METTL14 expression was significantly upregulated in TNBC tissues and cell lines. Silencing METTL14 significantly inhibited TNBC cell growth and invasion in vitro, as well as suppressed tumour growth. Mechanically, METTL14 was first found to activate miR-29c-3p through m6A and regulate tripartite motif containing 9 (TRIM9) to promote ubiquitination of pyruvate kinase isoform M2 (PKM2) and lead to its transition from tetramer to dimer, resulting in glucose metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to promote the progress of TNBC. Taken together, these findings reveal important roles of METTL14 in TNBC tumorigenesis and energy metabolism, which might represent a novel potential therapeutic target for TNBC.

Noncovalent interactions between biomolecules facilitated their application in food emulsions' construction: A review.

The use of biomolecules, such as proteins, polysaccharides, saponins, and phospholipids, instead of synthetic emulsifiers in food emulsion creation has generated significant interest among food scientists due to their advantages of being nontoxic, harmless, edible, and biocompatible. However, using a single biomolecule may not always meet practical needs for food emulsion applications. Therefore, biomolecules often require modification to achieve ideal interfacial properties. Among them, noncovalent interactions between biomolecules represent a promising physical modification method to modulate their interfacial properties without causing the health risks associated with forming new chemical bonds. Electrostatic interactions, hydrophobic interactions, and hydrogen bonding are examples of noncovalent interactions that facilitate biomolecules' effective applications in food emulsions. These interactions positively impact the physical stability, oxidative stability, digestibility, delivery characteristics, response sensitivity, and printability of biomolecule-based food emulsions. Nevertheless, using noncovalent interactions between biomolecules to facilitate their application in food emulsions still has limitations that need further improvement. This review introduced common biomolecule emulsifiers, the promotion effect of noncovalent interactions between biomolecules on the construction of emulsions with different biomolecules, their positive impact on the performance of emulsions, as well as their limitations and prospects in the construction of biomolecule-based emulsions. In conclusion, the future design and development of food emulsions will increasingly rely on noncovalent interactions between biomolecules. However, further improvements are necessary to fully exploit these interactions for constructing biomolecule-based emulsions.

Yigan Mingmu Decoction inhibits diabetic macular edema through regulating Kir4.1/AQP4 axis: a study based on network pharmacology.

OBJECTIVE: To explore the role and mechanism of Yigan Mingmu Decoction (YGMMD) in preventing and treating diabetic macular edema (DME). METHODS: The bioactive compounds in YGMMD and their targets were screened using network pharmacology. Sprague Dawley (SD) rats were treated with the respective drugs: andomine, YGMMD-L, YGMMD-M, YGMMD-H for four weeks. Blood glucose, body weight, and morphologic indicators were measured, and hematoxylin and eosin (H&E) staining was used to assess retinal pathologic changes. Western blotting was used to monitor the expression of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT), pathway-related proteins aquaporin 4 (AQP4), inwardly rectifying potassium channel subtype 4.1 (Kir4.1), and phosphorylase extracellular regulated protein kinases (p-ERK1/2). Immunofluorescence was used to observe the expression levels of AQP4 and Kir4.1. Immunohistochemistry was performed to determine the expression of p-ERK1/2. RESULTS: Pharmacologic network analysis and molecular docking suggested that YGMMD treatment of DME regulates AQP4/Kir4.1. In vivo experiments showed that YGMMD had significant hypoglycemic effects and reduced retinal edema in Sprague Dawley (SD) rats: YGMMD-H downregulated AQP4 and p-ERK1/2 and upregulated p-AKT and Kir4.1. Findings suggest that the therapeutic effect of YGMMD in DME is probably due to the deregulation of AQP4/Kir4.1 expression through the ERK1/2-PI3K-AKT pathway. CONCLUSION: This study shows that YGMMD inhibits the activation of p-ERK1/2 while concurrently enhancing the expression of p-AKT, leading to a decrease in AQP4 levels and the upregulation of Kir4.1 expression. As a result, the balance in the retinal fluid clearance system is restored, effectively alleviating DME.

Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα+) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα+ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Identification of a novel compound heterozygous pathogenic variant in MYO7A causing Usher syndrome type IB in a Chinese patient: a case report.

Herein, we report the clinical and genetic features of a patient with Usher syndrome type IB to improve our collective understanding of the disorder. The patient was a teenaged boy with congenital profound hearing loss, progressive visual loss, and vestibular hypoplasia; his parents were phenotypically normal. His pure tone audiometry hearing thresholds were 100 dB at all frequencies, and distortion product otoacoustic emission was not elicited at any frequencies in either ear. Moreover, an auditory brainstem response test at 100 dB normal hearing level revealed no relevant response waves, and a caloric test showed vestibular hypoplasia. Fundus examination revealed retinitis pigmentosa and a reduced visual field. The use of high-throughput sequencing technology to screen the patient's family lineage for deafness-related genes revealed that the patient carried a compound heterozygous pathogenic variant of MYO7A: c.541C > T and c.6364delG. This pathogenic variant has not previously been reported. Our findings may provide a basis for genetic counseling, effective treatment, and/or gene therapy for Usher syndrome.

AMPK Signalling Pathway: A Potential Strategy for the Treatment of Heart Failure with Chinese Medicine.

Heart failure (HF) is a complex clinical syndrome that represents the advanced stage of cardiovascular disease, characterized by systolic and diastolic dysfunction of the heart. Despite continuous updates in HF treatment drugs, the morbidity and mortality rates remain high, necessitating ongoing exploration for new therapeutic targets. Adenosine monophosphate-activated protein kinase (AMPK) is the serine/threonine protein kinase which responds to adenosine monophosphate (AMP) levels.Activation of AMPK shifts cellular metabolic patterns from synthesis to catabolism, enhancing energy metabolism in pathological conditions such as inflammation, ischemia, obesity, and aging. Numerous studies have identified AMPK as a vital target for HF treatment, with herbal monomers/extracts and compounds affecting key signaling factors including rapamycin targeting protein (mTOR), silencing regulator protein 1 (SIRT1), nuclear transcription factor E2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB) through regulation of the AMPK signaling pathway.This modulation can achieve the effects of improving metabolism, autophagy, reducing oxidative stress and inflammatory response in the treatment of heart failure, with the advantages of multi-targeting, comprehensive action and low toxicity.The modulation of the AMPK pathway by Traditional Chinese Medicine (TCM) has emerged as a crucial research direction for the prevention and treatment of HF, but a systematic summary and generalization in this field is lacking. This article provides an overview of the composition, regulation, and mechanism of the AMPK signaling pathway's influence on HF, as well as a summary of current research on the regulation of the AMPK pathway by TCM for HF prevention and treatment. The aim is to serve as a reference for the diagnosis and treatment of HF using TCM and the development of new drugs.

Chemical and spatial dual-confinement engineering for stable Na-S batteries with approximately 100% capacity retention.

Sodium-sulfur (Na-S) batteries are attracting intensive attention due to the merits like high energy and low cost, while the poor stability of sulfur cathode limits the further development. Here, we report a chemical and spatial dual-confinement approach to improve the stability of Na-S batteries. It refers to covalently bond sulfur to carbon at forms of C-S/N-C=S bonds with high strength for locking sulfur. Meanwhile, sulfur is examined to be S1-S2 small species produced by thermally cutting S8 large molecules followed by sealing in the confined pores of carbon materials. Hence, the sulfur cathode achieves a good stability of maintaining a high-capacity retention of 97.64% after 1000 cycles. Experimental and theoretical results show that Na+ is hosted via a coordination structure (N···Na···S) without breaking the C-S bond, thus impeding the formation and dissolution of sodium polysulfide to ensure a good cycling stability. This work provides a promising method for addressing the S-triggered stability problem of Na-S batteries and other S-based batteries.

Development and validation of a network calculator model for safety and efficacy after pancreaticoduodenectomy in the elderly patients with pancreatic head cancer.

BACKGROUND: Benefiting from increased life expectancy and improved perioperative management, more elderly patients with pancreatic head cancer (PHC) underwent pancreaticoduodenectomy (PD). However, individualized predictive models for the safety and efficacy of PD is still lacking. this study aimed to developed three safety- and efficacy-related risk calculators for elderly (> = 65 years) PHC patients. METHODS: This study was designed with two research cohorts, namely, the training cohort and the validation cohort, and comprises four general steps: (1) Risk factors were analyzed for the incidence of postoperative complications, cancer-specific survival (CSS), and overall survival (OS) in the training cohort (N = 271) using logistic and Cox-regression analysis. (2) Nomograms were then plotted based on the above results. (3) The accuracy of the developed nomogram models was then verified with the validation cohort (N = 134) data using consistency index (C-index) and calibration curves. (4) We then evaluated the efficacy of these nomograms using decision curve analysis (DCA) in both the training and validation cohorts, and ultimately constructed three online calculators based on these nomograms. RESULTS: We identified ASA, diabetes, smoking, and lymph node invasion as predisposing risk factors for postoperative complications, and the predictive factors that affected both OS and CSS were ASA, diabetes, BMI, CA19-9 level, and tumor diameter. By integrating the above risk factors, we constructed three nomograms on postoperative complication, CSS, and OS. The C-index for complication, CSS, and OS were 0.824, 0.784, and 0.801 in the training cohort and 0.746, 0.718, and 0.708 in the validation cohort. Moreover, the validation curves and DCA demonstrated good calibration and robust compliance in both training and validation cohorts. We then developed three web calculators (https://caiming.shinyapps.io/CMCD/, https://caiming.shinyapps.io/CMCSS/, and https://caiming.shinyapps.io/CMOS/) to facilitate the use of the nomograms. CONCLUSIONS: The calculators demonstrated promising performance as an tool for predicting the safety and efficacy of PD in elderly PHC patients.