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*

Objective:To establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium and evaluate its quality. Method:According to the preparation conditions of the standard decoction,15 batches of standard decoction of Citri Reticulatae Pericarpium were prepared.HPLC was employed to determine the content of hesperidin in this standard decoction.Ultraviolet spectroscopy(UV) and infrared spectroscopy(IR) were used to establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium.The correlation coefficient method and double index sequence analysis method were used to compare and analyze the spectra of different batches of this standard decoction. Result:The content of hesperidin in 15 batches of this standard decoction were 0.82%-2.60%,and the measured value of dry extract rate was 32.02%-46.11%.Compared with ultraviolet and infrared control fingerprint,the fingerprint similarities of the standard decoction of each batch were > 0.897 and > 0.942,respectively.The double index analysis results showed that the common peak ratio was more than 62.50%,variation peak ratio was less than 46.67%. Conclusion:The quality evaluation method established in this study can be used for systematic evaluation of standard decoction of Citri Reticulatae Pericarpium,and it can provide theoretical reference for the formulation of quality standard of Citri Reticulatae Pericarpium dispensing granules and other related preparations.

ObjectiveTo evaluate the efficacy of mini-incisional double-tsuge suture method with 0-0 absorbable polydioxanone-cord (PDS-Ⅱ)in repair of acute achilles tendon rupture.MethodsA total of 34 patients were subjected to acute closed achilles tendon ruptures,including 25 males and 9 females at a mean age of 32 years ( range,20-45 years).Injury causes included sports injuries in 27 patients,falling injuries in six and heavy object impingement injury in one.The time from injury to operation was average 3 days (range,1-6 days).All patients underwent minimally invasive repair with double-tsuge suture method by using PDS-Ⅱ.The ankle joint was fixed with short leg plaster cast at 30° plantar flexion position and the cast was removed six weeks later to take functional exercise.The patients could walk with full weight-bearing 8-10 weeks later and could gradually return to activity 3-4 months later.Results There was one patient with poor incision healing and one patient with reflex sympathetic dystrophy postoperatively.The rest patients had stage Ⅰ incision healing without skin adhesions.No complications such as infection,lower extremity deep venous thrombosis or sural nerve injury occurred postoperatively.All the patients received follow-up of 12-24 months (average 15 months),which showed no complications like tendon rerupture occurred.According to clinical evaluation criterion of Termann,the average score was 92 points (range,76-96 points).The result was excellent in 28 patients,good in five and fair in one,with excellence rate of 97％.ConclusionsSmall incisional double-tsuge suture method achieves low rate of complications and good outcomes for repairing acute achilles tendon rupture and is an ideal tendon surgery approach.

Objective To investigate the expression and significance of the endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and vascular endothelial growth factor(VEGF) in adrenocortical lesions of primary aldosteronism. Methods The expressions of EG-VEGF, and VEGF were detected by immunohistochemistry and real-time fluorescence quantitative PCR in samples of 18 cases of adrenocortical adenoma, 6 adrenocortical hyperplasia, and 8 normal adrenal cortex. The correlation between the expressions of EG-VEGF, VEGF, and clinicopathological parameters was analyzed. Results The expression of EG-VEGF or VEGF in adrenocortical adenomas was higher than that in adrenocortical hyperplasia or normal adrenal cortex ( all P＜0. 05 ), and the expression of EG-VEGF or VEGF between adrenocortical hyperplasia samples and normal adrenal cortex samples was indistinctive. There was no statistically significant correlation between EG-VEGF or VEGF expression and sex, age, blood pressure, serum potassium, plasma renin activity, except in case of serum aldosterone( P＜0.05 ). A positive correlation between EG-VEGF and VEGF ( P＜0. 01 ) was found. Conclusions EG-VEGF and VEGF may play a significant role in the formation and development of adrenocortical tumors in primary aldosteronism.

BACKGROUND: Secretion of various neurotrophic factors by Schwann cells plays important roles in neural regeneration. However, the secretion capability is affected by many factors. To seek a feasible method for promoting nerve growth factor secretion by Schwann cells is a key of regeneraion following neurologic defect.OBJECTIVE: To explore the effects of methylprednisolone(solu-medrol) on the secreted function of Schwann cells of cultured rats.METHODS: Schwann cells were isolated and cultured by enzyme digestion method. Cell growth was observed under an inverted phase contrast microscope. Following passage, purity of some Schwann cells was identified using S-100 protein immunity. Other Schwann cells were regulated using cell counting plate into 1×10~9/L, and incubated in a 6-well culture plate (15 wells) for further incubation. Following 4 days of culture, different concentrations of solu-medrol (10~(-3), 10~(-4), 10~(-6), 10~(-8) mol/L) were administrated to the cell, while blank control group (1 well) was given no drug. 24, 48 and 72 hours after administration, reverse trancription-polymerase chain reaction (RT-PCR) was used in the detection of the levels of nerve growth factor mRNA.RESULTS AND CONCLUSION: Number of primarily cultured cells was significantly increased at day 7, and 80% cells were confluent. Subcultured cells were spindle-shaped, with 2 thin long processes, showing positive fluorescence staining. Fibroblasts were round or flat, showing negative reaction of fluorescence staining. Reserve transcription-polymerase chain reaction demonstrated that nerve growth factor number at 72 hours affected by 10~(-8) mol/L radiosone was increased compared with the blank control group and other concentrations and other time points (P < 0.05). Number of nerve growth factor was reduced following treatment of 10~(-3) mol/L radiosone compared with the blank control group and other concentrations (P < 0.05). These results suggested that high concentration of solu-medrol prohibits secreted function of Schwann's cells, but long time and low dosage solu-medrol promotes secreted function of Schwann's cells.

ObjectiveTo study the characteristic of apoptosis and the expression of inducible nitric oxide synthase(iNOS),as well as relation between them after spinal cord injury (SCI) in rats.Methods84 adult SD rats were randomly divided into three groups,and made into mild,moderate and severe acute SCI models.The rats were killed at 4h,8h,1d,3d,7d,14d and 21d after surgery.The histopathology changes in spinal cord tissue were observed with HE staining microscopic examination.The expression of iNOS was determined by immunohistochemistry and the apoptosis was labeled by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL).ResultsThe histopathology changes in spinal cord tissue deteriorated with increasing in injury degree.A little iNOS immunoreactivity (iNOS-IR) was detected in nerve cells,gliocytes,ependymocytes and blood vessel endotheliocytes of normal and vertebra shelf operated controls,increasing at 8 h, and in flood tide in 7 d. The expression of Bax and the rates of TUNEL positive cells were similar with that of iNOS after SCI. There was positive correlation between expression of iNOS and degree of primary SCI ,apoptosis index(r=0.414,P<0.01;r=0.854,P<0.01).Conclusions Expression of iNOS and Bax increase and a large number of TUNEL positive cells present after SCI in rats. There is positive correlation between expression of iNOS and degree of primary SCI,apoptosis index.