Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.
Humans ; Mutation/genetics* ; Neoplasms/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Animals

Objective: To investigate the mental health status and related factors among primary and secondary school students in western Yunnan Province, so ao to provide scientific evidences for advancing mental health education. Methods: In June 2024, a stratified cluster sampling method was employed to select 4 584 students from 18 schools across Diqing Tibetan Autonomous Prefecture, Lincang City and Baoshan City three regions in western Yunnan Province. The Mental Health Test (MHT) was used for assessment. Latent class analysis (LCA) and Logistic regression were applied for data classification and related factor analysis respectively. Results: The overall positive detection rate of MHT was 11.81%, with a mean total score of 40.50±19.25. The predominant issues were learning anxiety (58.4%), hypersensitivity tendency (31.1%), and self blame tendency (23.1%). LCA categorized students into four groups:severe psychological problems group (74.4% detection rate), learning anxiety hypersensitivity group ( 16.4 %), learning anxiety physical symptoms group (9.2%), and healthy group (0). Logistic regression revealed that compared with the healthy group, the severe problems group showed higher risks among females ( OR =3.01), junior/senior high school students ( OR =1.88/4.02), and those with authoritarian parenting ( OR =3.54); the anxiety hypersensitivity group had higher risks for females ( OR =1.87), senior high students ( OR =1.54), boarders ( OR =1.31), and authoritarian parenting recipients ( OR = 1.85 ); the anxiety physical symptoms group demonstrated increased risks among females ( OR =2.22), senior high students ( OR =2.58), and authoritarian parenting recipients ( OR =2.74), while lower risks were observed for students with parent/grandparent guardians ( OR =0.38) and non only children ( OR =0.58) (all P <0.05). Conclusions Mental health problems are prominent among students in western Yunnan, with gender, grade level, boarding status, guardian type, and parenting style being key determinants. Recommendations include strengthening mental health education, prioritizing left behind children s psychological well being and promoting healthy development.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective:To systematically evaluate the efficacy, patient-reported outcomes (PROs) and safety of hyaluronic acid (HA) fillers and collagen stimulators (PCL/PLLA) for various facial aesthetic indications.Methods:This study focused on facial fillers approved and widely used in China, including HA fillers such as Juvéderm?, Restylane?, Belotero?, Fillmed?, and PCL/PLLA such as Ellansé?, L?viselle?, and CureWhite?. A systematic literature search was conducted across both English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, and Wanfang Data, covering the period from database inception to August 24, 2023, to identify randomized controlled trials (RCTs). The characteristics and outcomes of the included RCTs were summarized and analyzed, including efficacy indicators by injection site, patient satisfaction, and safety profiles. Network meta-analysis (NMA) was performed using R software to compare efficacy outcomes, including the 6-month improvement response rate for nasolabial folds (NLF) and the global aesthetic improvement scale (GAIS).Results:A total of 38 articles were included. Among them, Juvéderm? was most frequently used as the treatment group (17 out of 38 articles), while Restylane? was the most common comparator (17 out of 38 articles), particularly in studies involving NLF injections (15 out of 16 articles). For collagen stimulators, only 2 studies on Ellansé? were included, both focusing solely on NLF treatment. Quality assessment showed that 34 studies were of medium to high quality, with Juvéderm? accounting for the majority of high-quality studies (11 articles). Based on injection sites, NLF was the most studied area (16 articles), followed by the midface (8 articles), and the remaining 14 articles covered other regions including lips, nose, chin, and infraorbital area. In the NLF region, the 6-month improvement response rate assessed by blinded investigators showed that Juvéderm? showed better outcomes than Restylane? ( RR=1.07, 95% CI: 0.89-1.32), while Belotero? was slightly inferior to Restylane? ( RR=0.97, 95% CI: 0.65-1.44), although the differences were not statistically significant. Subject-reported outcomes showed consistent trends with investigator assessments. For 6-month GAIS improvement, Juvéderm? and Restylane? showed comparable result within the HA filler category ( RR=1.01, 95% CI: 0.71-1.43). The collagen stimulator Ellansé? demonstrated numerically higher values than HA fillers ( RR=1.32, 95% CI: 0.86-2.08). However, none of these differences reached statistical significance. In midface treatments, Juvéderm? had more long-term evidence, with follow-up periods extending up to 24 months. Four studies reported numerically greater volume enhancement with Juvéderm? compared to Restylane?. For other facial areas, Juvéderm? had the most comprehensive clinical evidence, covering the widest range of injection sites. No relevant RCTs were available for collagen stimulators in these regions. Regarding patient satisfaction, 19 studies reported patient-reported outcomes, with Juvéderm? contributing 16 of them, and showing higher satisfaction in 6 head-to-head comparisons with Restylane?. In contrast, collagen stimulators currently lack such evidence. Safety result indicated that HA fillers were generally safe and well tolerated, while safety data for collagen stimulators remain limited due to insufficient high-quality evidence. Conclusion:Among the HA fillers, Juvéderm? has a large quantity and highest quality of clinical studies, and NMA result shows its superior efficacy in NLF. In comparison, the current evidence is still not sufficient to draw a clear conclusion for the PCL/PLLA due to a lack of adequate high-quality clinical evidence regarding its clinical efficacy, PROs, and safety.

Objective Based on the sampling test of national drugs,the quality of Huatan Pingchuan tablets was systematically evaluated,and the quality problems were analyzed to provide references and suggestions for the quality control of this variety and to improve its quality standard.Methods A total of 157 batches of samples were tested according to the statutory standard,and based on the testing results and prescription characteristics,microscopic identification and comprehensive analysis of its quality using thin-layer chromatography,high-performance liquid chromatography,and other methods were subsequently established or improved for the exploratory research.Results The established thin-layer chromatography identification for Radix Scutellariae,as well as the content determination methods for Radix Scutellariae,Syringae Cortex,and promethazine hydrochloride,are easy to operate and have good durability and specificity and can be applied to the quality control and evaluation of Huatan Pingchuan tablets.Conclusions The overall quality of the tablets is average;some enterprises should strengthen the quality control of raw medicinal materials(decoction pieces);individual enterprises have significant differences in the quality of samples from different batches,so they need to pay attention to the quality of raw materials and the stability of production processes;the inspection items of the current standards cannot fully reflect the key quality attributes of drugs,and standards improvement work needs to be carried out.