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 study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective:To evaluate the effect of evidence-based nursing practice for functional rehabilitation of post-stroke neurogenic bladder (PSNB) .Methods:From October 2020 to July 2021, 136 PSNB patients admitted to the Department of Neurology, Jiangyin People's Hospital were selected by convenience sampling as the research object. According to the random number table method, the patients were divided into the study group and the control group, with 68 cases in each group. The control group received routine rehabilitation nursing, while the study group was given evidence-based rehabilitation nursing based on the control group. The urodynamics, rates of bladder balance, urinary incontinence and urinary retention after intervention were compared between the two groups.Results:After three months of intervention, bladder compliance and bladder balance rate in the study group were higher than those in the control group, and the residual urine volume was less than that in the control group, with statistical differences ( P<0.05) . After three months of intervention, urinary retention rate in the study group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Evidence-based rehabilitation nursing can help to promote the rapid recovery of bladder balance in PSNB patients and improve the prognosis of patients.

Objective:To investigate the clinical efficacy of dual growing rods (DGR) in the treatment of early onset scoliosis (EOS), and to evaluate the safety of its clinical application.Methods:From March 2015 to August 2021, a total of 20 EOS patients with onset age within 10 years old who were treated with dual growth rod technique were retrospectively analyzed, including 8 males and 12 females. The mean age of patients at first surgery was 9.0±1.4 years (range, 6.3-10.8 years); the preoperative Cobb angle was 59.0°±16.8° (range, 41.2°-103°). The Cobb angle, thoracic kyphosis angle, lumbar lordosis angle, T 1-T 12 height, T 1-S 1 height, coronal plane imbalance, sagittal vertical axis (SVA), apical vertebral translation (AVT) and Campbell's space available for lung ratio (SAL) were recorded and analyzed while surgery-related complications were also recorded. Results:The average follow-up time of 20 patients was 28.07±14.30 months. The average initial hospital stay was 20.56±8.28 days, the average initial operation time was 211.70±39.80 min, the average blood loss in the initial operation was 255.00±149.50 ml, and the average surgical distraction was 1.60±0.51 times per person. The Cobb angle of the main curve in the coronal plane decreased from 59.00°±16.80° before operation to 33.40°±11.80° after the initial operation, which was 29.67°±11.67° at 1 year and 29.40°±11.30° at the last follow-up. Preoperative thoracic kyphosis angle was 41.39°±6.06°, decreased to 31.72°±3.56° after the initial operation, was 30.32°±4.26° at 1-year and 30.24°±4.23° at the last follow-up; preoperative lumbar lordosis angle was 45.90°±8.03°, decreased to 42.65°±9.05° after initial operation, 41.55°±7.84° at 1-year follow-up, and 41.53°±8.21° at the last follow-up; preoperative T 1-S 1 height was 31.76±4.42 cm, initial after operation, it increased to 34.64±3.96 cm, 36.73±3.87 cm at 1 year, and 37.28±4.36 cm at the last follow-up; preoperative T 1-T 12 height was 17.38±2.76 cm. increased to 19.39±2.86 cm after the initial operation, 21.77±2.71 cm at 1 year, and 21.91±2.74 cm at the last follow-up; Preoperative coronal balance was 1.52±0.73 cm, and decreased to 0.87±0.38 cm after the initial operation, 0.81±0.38 cm at 1 year, and 0.77±0.37 cm at the last follow-up; preoperative sagittal balance was 1.94±0.78 cm, and 1.42±0.56 cm after operation, 1.28±0.55 cm at 1 year, and 1.26±0.57 cm at the last follow-up; The preoperative apical vertebra offset was 4.33±1.85 cm, and 2.16±1.47 cm after the initial operation, 1.63±1.17 cm at 1 year, and 1.61±1.23 cm at the last follow-up; SAL increased from preoperative 0.88±0.05 to 0.94±0.03 postoperatively, and 0.96±0.01 at 1-year follow-up, and 0.97±0.01 at the last follow-up. The differences between the above indicators before and after surgery were statistically significant ( P<0.05); there was a statistically significant difference in SAL between the 1-year follow-up and the last follow-up ( t=3.80, P=0.001), and other indicators were not statistically significant. Among the 20 cases, there were 5 cases of postoperative complications, including 2 cases of pedicle screw loosening and displacement, 2 cases of transverse process hook decoupling, and 1 case of proximal junctional kyphosis (PJK). The complication rate was 25% (5/20), all of them underwent revision treatment, and the prognosis was good after timely treatment. Conclusion:The dual growth bar technique can effectively control the progression of EOS deformity, preserve the longitudinal growth potential of the spine, and buy time for the development of the thorax in children, which has high safety.

Aquatic plants and the epiphytic microorganisms are important contributors to the purification of constructed wetlands. Taking the dragon-shaped water system of Beijing Olympic Park as a model, this study analyzed the structure and function of the microbial communities reside the sediment, the water body and the rhizosphere and phyllosphere of three submerged plants-Vallisneria natans, Myriophyllum verticillatum, and Potamogeton pectinatus using high-throughput sequencing technology. The results showed that the microbial diversity from the highest to the lowest were samples from sediment, plant rhizosphere, plant phyllosphere and water. The microbial diversity of plant phyllosphere samples were significantly higher than those of the water body. LEfSe analysis showed that different habitats enriched different microbial groups. The sediments mainly enriched anaerobic microbes, while the water body and the phyllosphere of plants mainly enriched aerobic microbes, and the rhizosphere of plants had the both. Functional prediction analysis showed that the abundance of denitrification marker genes in phyllosphere samples was higher than that in samples from rhizosphere, sediment and water body, and the abundance of denitrification marker genes in phyllosphere samples of M. verticillatum and P. pectinatus was higher than that of V. natans. This study could serve as a guidance for the selection of submerged plants and functional microorganisms for constructed wetlands.
Beijing ; Hydrocharitaceae ; Microbiota ; Rhizosphere ; Water

Objective To explore the clinical new ways to repair the soft tissue defect of upper lip.Methods The soft tissue defect of upper lip caused by various reason were repaired with the buccal region of nasolabial groove flap.The size of flap was designed based on the range of soft tissue defect and located in the buccal region along nasolabial groove.The maximum scale of flaps between the length and width were 2∶1 and slit to the SMAS layer.The soft tissue defect of upper lip was repaired by direct vicinity aversion of the flap.The wound after the flap diversion was direct sut in favour of propulsion of the flap and relief the tension of flap pedicle.Results The flaps completely survived in 15 cases without obviously scar accrementition.The cosmetic result were satisfactory.Conclusion The buccal region of nasolabial groove flap is characterized by simple designation,easy dissection,reliable blood supply with the vascular net of fascia without well-known blood vessel damaged and repaired by direct vicinity aversion.Therefore,it is an ideal new method to repair the soft tissue defect of upper lip.