The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To investigate the effects of the expanded lateral thoracic artery perforator flap in the reconstruction of breast scar contracture deformity after burns in minor females.Methods:The study was a retrospective observational study. From July 2018 to October 2023, 8 female children aged 4 to 12 years and with breast scar contracture deformity after burns, who met the inclusion criteria, were admitted to the Department of Burns and Plastic Surgery of Guangzhou Red Cross Hospital of Jinan University. The skin and soft tissue expander (hereinafter referred to as expander) was placed in the first stage. The contracture scar was removed and released in the second stage, and the wound formed after the scar was removed measured between 9 cm×8 cm and 15 cm×10 cm. The expanded lateral thoracic artery perforator flap was designed and transferred to repair the wound with resected flap area of 10 cm×9 cm to 16 cm×11 cm, and the wound at the flap donor area was directly sutured. The complications such as incision infection, hematoma, and expander exposure were observed after stage Ⅰ surgery. After stage Ⅱ surgery, the survival of the flap and the wound healing at the flap donor area were observed. During the 1-year follow-up after the stage Ⅱ surgery, the breast development was evaluated according to tanner staging performance of female pubertal breast development, the aesthetic effect of the affected breast was evaluated by using the aesthetic effect evaluation standard after breast surgery, the Vancouver scar scale (VSS) was used to score the scar condition at the flap donor and recipient areas, and the satisfaction of the children's families with the surgical outcomes was investigated by using a self-made scale.Results:After stage Ⅰ surgery, no incision infection, hematoma, expander exposure, or other complications occurred in 8 children. After stage Ⅱ surgery, only one child had tissue necrosis at the distal end of the flap with a size of about 2 cm×1 cm, which healed after dressing change, and the flap in other children had good blood supply, soft texture, moderate thickness, and similar color to the skin at the recipient area. The wounds at all flap donor areas healed well. During the 1-year follow-up after stage Ⅱ surgery, 7 children had normal breast development, with their breast volume, height, and shape being almost the same as or similar to the healthy side, with the aesthetic effect of all being grade Ⅰ; the breast in one child had not yet developed, and these indicators were not evaluated. The locations of nipple areola complex in 8 children were almost the same as or similar to those in the healthy side, and their skin color, integrity, texture, and elasticity of the partial breast repaired by the transferred flap were similar to those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The shapes of nipple and areola in 5 children were inconsistent with those in the healthy side because of the original scar, with the aesthetic effect of all being grade Ⅱ, and the shapes of nipple and areola in the other 3 children were consistent with those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The VSS score of the scar at the flap recipient area was 2-5, and the VSS score of the scar at the flap donor area was 1-3. Seven children's families were satisfied with the surgical effect, and one child's family was basically satisfied with the surgical effect.Conclusions:For the breast scar contracture deformity of minor females after burns, the expanded lateral thoracic artery perforator flap is used for reconstruction before puberty, which results in fewer postoperative complications, good breast shape, and hidden scar at the flap donor area. It is beneficial for the normal development of adolescent breasts, and is one of the safe and effective methods for the treatment of breast scar contracture deformity in minor females after burns.

Objective To evaluate the efficacy of minimally invasive neuroendoscopy combined with intraventricular drainage in the treatment of intraventricular hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 88 patients with intraventricular hemorrhage who underwent surgical treatment from January 2018 to December 2023.All patients received bilateral ventricular indwelling external drainage tubes.Among them,37 cases were included in the endoscopy group.The bleeding side or side with more blood accumulation underwent a midline fistula.With the assistance of neuroendoscopy,the intraventricular blood clots were removed and a ventricular drainage tube was inserted.The contralateral ventricle was punctured and a ventricular drainage tube was inserted;The remaining 51 cases were included in the drainage group,in which bilateral ventricular drainage tubes were placed according to the traditional intraventricular drainage protocol.Results There was no significant statistical difference(P>0.05)between the endoscopic group and the drainage group in terms of mortality rate(10.8%vs.13.7%),rebleeding rate(8.1%vs.11.8%,P=0.576),intracranial infection rate(10.8%vs.17.6%,P=0.372),and hydrocephalus rate(10.8%vs.23.5%,P=0.166).Similarly,no significant statistical difference was found in the total hospitalization cost between the endoscopy group and the drainage group[(90700±73000)yuan vs.(99500±66000)yuan]and the GOS score during the 6-month follow-up(3.16±1.14 vs 3.02±1.12)showed(P>0.05).However,the postoperative GCS score improvement was significantly better in the endoscopic group than in the drainage group[2.00(2.00,4.00)vs.1.00(0.00,3.00),P=0.002].The duration of the extracranial drainage catheter placement was significantly shorter in the endoscopic group than in the drainage group[(7.16±2.99)days vs.(10.12±3.93)days,P<0.001].Conclusion Neuroendoscopy-assisted evacuation of intraventricular hemorrhage facilitates effective hematoma clearance,reduces the duration of ventricular drainage catheterization,and may contribute to improved patient outcomes.

Objective To evaluate the efficacy of minimally invasive neuroendoscopy combined with intraventricular drainage in the treatment of intraventricular hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 88 patients with intraventricular hemorrhage who underwent surgical treatment from January 2018 to December 2023.All patients received bilateral ventricular indwelling external drainage tubes.Among them,37 cases were included in the endoscopy group.The bleeding side or side with more blood accumulation underwent a midline fistula.With the assistance of neuroendoscopy,the intraventricular blood clots were removed and a ventricular drainage tube was inserted.The contralateral ventricle was punctured and a ventricular drainage tube was inserted;The remaining 51 cases were included in the drainage group,in which bilateral ventricular drainage tubes were placed according to the traditional intraventricular drainage protocol.Results There was no significant statistical difference(P>0.05)between the endoscopic group and the drainage group in terms of mortality rate(10.8%vs.13.7%),rebleeding rate(8.1%vs.11.8%,P=0.576),intracranial infection rate(10.8%vs.17.6%,P=0.372),and hydrocephalus rate(10.8%vs.23.5%,P=0.166).Similarly,no significant statistical difference was found in the total hospitalization cost between the endoscopy group and the drainage group[(90700±73000)yuan vs.(99500±66000)yuan]and the GOS score during the 6-month follow-up(3.16±1.14 vs 3.02±1.12)showed(P>0.05).However,the postoperative GCS score improvement was significantly better in the endoscopic group than in the drainage group[2.00(2.00,4.00)vs.1.00(0.00,3.00),P=0.002].The duration of the extracranial drainage catheter placement was significantly shorter in the endoscopic group than in the drainage group[(7.16±2.99)days vs.(10.12±3.93)days,P<0.001].Conclusion Neuroendoscopy-assisted evacuation of intraventricular hemorrhage facilitates effective hematoma clearance,reduces the duration of ventricular drainage catheterization,and may contribute to improved patient outcomes.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.