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 evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.

Objective:To explore the changes in early postpartum pelvic floor muscle strength following the implementation of the new labor process.Methods:This retrospective cohort study selected 1 834 primiparous women with singleton, full-term pregnancies who delivered at Peking University First Hospital from February 2011 to March 2016 and had a pelvic floor re-examination 6-8 weeks postpartum. Out of these, 738 cases who followed the old labor process before 2014 were categorized as the old process group, and 1 096 cases who followed the new labor process after 2014 were categorized as the new process group. Basic data, childbirth information, and postpartum pelvic floor muscle strength of the two groups were compared. Data were statistically analyzed using t-test, Chi-square test, Mann-Whitney U test, Wilcoxon rank-sum test, and ordered multicategory logistic regression to assess the impact of the new and old labor process and other factors on pelvic floor muscle strength. Results:The total duration of labor, as well as the duration of the first, second, and third stages of labor, were longer in the new process group than in the old process group [549.0 min (360.0-768.0 min) vs. 482.5 min (328.0-635.0 min), 465.0 min (297.5-672.5 min) vs. 420.0 min (285.0-555.0 min), 42.0 min (24.0-74.0 min) vs. 27.0 min (18.0-45.0 min), with Z-value of－5.72,－3.95, and－9.28, all P<0.05). The rates of vaginal delivery and labor analgesia were higher in the new process group [72.1% (790/1 096) vs. 67.2% (496/738), χ2=7.41; 67.4% (739/1 096) vs. 53.4% (394/738), χ2=36.82; both P<0.05]. There were no statistically significant differences in the comparison of Class Ⅰ and Class Ⅱ muscle strength grades between the two groups (all P>0.05). Conclusion:There was no significant decline in early postpartum pelvic floor muscle strength following the implementation of the new labor process standards.

Objective:To investigate the effect of six degree of freedom (6-DOF) bed combined with cone beam computed tomography (CBCT) in the on-line correction of setup errors in patients with primary rectal cancer.Methods:The clinicopathological data of 17 patients with primary rectal cancer in Department of Radiotherapy, Third Hospital of Peking University from July 2013 to January 2014 were collected. There were 14 males and 3 females, a median age of 65 years. The difference of CBCT and 6-DOF bed combined with CBCT online correction of patients with positioning error were retrospectively analyzed.Results:Before position correction, the first CBCT verification of setup errors in the three translation directions including X (left and right), Y (in and out) and Z (up and down) directions were (0.06±0.25) cm, (0.13±0.40) cm and (-0.28±0.31) cm, respectively. The setup errors of RX (rotation pitch), RY(rolling) and RZ (left and right rotation) directions were (0.62±1.15)°, (-0.19±0.99)°, and (-0.34 ± 0.84)°, respectively . After correction of IGRT combined with six freedom of bed, the setup errors of translation X, Y and Z were (0.01±0.09) cm, (-0.01±0.05) cm and (-0.03±0.08) cm, respectively, and the setup errors of rotation RX, RY and RZ directions were (-0.16±0.40)°, (0.36±0.31)°and (-0.01±0.25)°, respectively. There were significant differences in translation direction (X, Y and Z direction) and rotation direction (Rx, RY and RZ) before and after 6-DOF bed combined with CBCT correction (all P<0.05). In the translation direction, the higher frequency range of Z-direction error value was 0.20-0.79 cm. In the rotation direction, the frequency range of error in Rx direction was 0.20°-2.99°. There was no significant difference between bone mode and gray scale model registration ( P>0.05). With the progress of radiotherapy, the setup errors of X, Z, Rx, RY and RZ directions increased except Y direction. Conclusions:In radiotherapy, six freedom bed combined with CBCT is helpful to correct the setup errors of patients with primary rectal cancer. Six freedom bed may be used to correct the setup errors of patients with primary rectal cancer online. Image-guided radiation therapy (IGRT) is recommended for bone pattern registration in patients with rectal cancer.

Objective:To investigate the effect of six degree of freedom (6-DOF) bed combined with cone beam computed tomography (CBCT) in the on-line correction of setup errors in patients with primary rectal cancer.Methods:The clinicopathological data of 17 patients with primary rectal cancer in Department of Radiotherapy, Third Hospital of Peking University from July 2013 to January 2014 were collected. There were 14 males and 3 females, a median age of 65 years. The difference of CBCT and 6-DOF bed combined with CBCT online correction of patients with positioning error were retrospectively analyzed.Results:Before position correction, the first CBCT verification of setup errors in the three translation directions including X (left and right), Y (in and out) and Z (up and down) directions were (0.06±0.25) cm, (0.13±0.40) cm and (-0.28±0.31) cm, respectively. The setup errors of RX (rotation pitch), RY(rolling) and RZ (left and right rotation) directions were (0.62±1.15)°, (-0.19±0.99)°, and (-0.34 ± 0.84)°, respectively . After correction of IGRT combined with six freedom of bed, the setup errors of translation X, Y and Z were (0.01±0.09) cm, (-0.01±0.05) cm and (-0.03±0.08) cm, respectively, and the setup errors of rotation RX, RY and RZ directions were (-0.16±0.40)°, (0.36±0.31)°and (-0.01±0.25)°, respectively. There were significant differences in translation direction (X, Y and Z direction) and rotation direction (Rx, RY and RZ) before and after 6-DOF bed combined with CBCT correction (all P<0.05). In the translation direction, the higher frequency range of Z-direction error value was 0.20-0.79 cm. In the rotation direction, the frequency range of error in Rx direction was 0.20°-2.99°. There was no significant difference between bone mode and gray scale model registration ( P>0.05). With the progress of radiotherapy, the setup errors of X, Z, Rx, RY and RZ directions increased except Y direction. Conclusions:In radiotherapy, six freedom bed combined with CBCT is helpful to correct the setup errors of patients with primary rectal cancer. Six freedom bed may be used to correct the setup errors of patients with primary rectal cancer online. Image-guided radiation therapy (IGRT) is recommended for bone pattern registration in patients with rectal cancer.

Objective To explore the feasibility of the perforator-based intermediate dorsal pedal flap with vessels of cutaneous nerve nutrition for repair of soft tissue defects of the forefoot.Methods A retrospective case series study was performed for seven cases of soft tissue defects of the forefoot hospitalized between February 2013 and January 2017.There were five males and two females,with a mean age of 38 years (range,18-73 years).Injury regions were lateral plantar skin defect in the forefoot in three cases,dorsal skin defect in the third webbed toe in two cases and proximal dorsal skin defect in the fourth toe in two cases.The defect area was about 2.5 cm × 1.5 cm-4.5 cm × 2.0 cm.The perforator-based intermediate dorsal pedal flap with vessels of cutaneous nerve nutrition was designed on the lateral dorsum of the foot and then was incised and transferred to repair the forefoot wound based on its surgical anatomy.The time of surgery and the amount of intraoperative blood loss were recorded.An observation was done on feeling,appearance,texture,blood supply and survival of the flap as well as swelling,hypertrophic scar,itching,paralysis of the skin grafting area.The recovery of the activity function was assessed by American Orthopedic Foot & Ankle Society (AOFAS) score.Results The surgery time was 1.0-1.5 h (mean,1 h),and intraoperative bleeding was about 50 ml (range,30-100 ml).Seven cases of perforator-based dorsal medial skin flap with vessels of cutaneous nerve nutrition all survived,with early wound healing.After 2 to 15 months follow-up,two-point discrimination of flaps was 9-15 mm(average,12.5 mm).Skin flaps were with excellent texture and without swelling,the color of which was close to normal color with good appearance.The postoperative foot did not have bone resorption,wound infection,tendon adhesion,line-type or flaky scar left locally,lower limb walking dysfunction or other complications.Patients were satisfied with the functions of donor and recipient sites and the appearance of the flap.Conclusions Perforation-based dorsal flap with vessels of cutaneous nerve nutrition has high survival rate,satisfaction of appearance and fast recovery of recipient site,with no obvious foot pain,limitation of joint movement or other complications,and therefore is a reliable method to repair soft tissue defects in forefoot.

Objective: To investigate the morphological characters of the dorsal perforators originated from the deep palmar arch, so as to provide anatomic basis for V-Y advanced perforator flap. Methods: The following contents were investigated in 30 adult hand specimens perfused with red latex under surgical magnifier: ①The origin, courses, branches and distribution of the dorsal perforators originatedd from the deep palmar arch. ②The characters of anastomosis among the dorsal perforators, the dorsal carpal and metacarpal arteries. Mimic operation was performed on another fresh specimens perfused with red latex. Results: There were three perforators originated from the deep palmar arch, which passed through the 2nd-4th dorsal interossei and then divided into an ascending branch and a descending branch at the dorsum of hand. Then the ascending branch anastomosed with the dorsal carpal artery, and the descending branch stretched to the 2nd-4th dorsal metacarpal arteries. The originating outer diameters of the 1st-3rd perforators were (1.1±0.2) mm, (0.9±0.3) mm and (0.7±0.1) mm respectively, and the length of the stems were (1.1±0.3) cm, (1.0±0.2)cm and (0.9±0.1) cm respectively. Conclusions The V-Y advanced perforator flap with the dorsal perforator of the deep palmar arch as its vascular pedicle could be used to repair the dorsal carpal or dorsal metacarpal soft tissue defects.

Objective To investigate the role of Stat1 gene in the proliferation and chemotherapeutic sensitivity of cervical cancer HeLa cells. Methods The protein expression of Stat1 in the Hela cells exposed to gradient concentrations of cisplatin (DDP) was detected by Western blotting with or without small interfering RNA (siRNA)-mediated Stat1 gene silencing. The effect of Sata1 silencing on the sensitivity to DDP and cell proliferation of the cells was tested using MTT assay and BrdU assay, and the expression of c-Myc was detected by Western blotting in the cells treated with siRNA and DDP. Results The expression of Stat1 in Hela cells exposed to DDP increased with the DDP concentrations, reaching 1.5 folds of the baseline at a DDP concentration of 5 mg/L and 2 folds at 10 mg/L. Stat1-siRNA effectively reduced Stat1 expression in Hela cells, promoted the cell proliferation, and enhanced the expression of c-Myc;DDP inhibited the cell growth and down-regulated c-Myc expression. Stat1-siRNA rescued DDP-induced inhibition of cell growth and c-Myc down-regulation. Conclusion The expression of Stat1 is associated with DDP sensitivity in cervical cancer cells, and Stat1 silencing can increase the sensitivity to DDP and c-Myc expression of the cells.

Objective To investigate the role of Stat1 gene in the proliferation and chemotherapeutic sensitivity of cervical cancer HeLa cells. Methods The protein expression of Stat1 in the Hela cells exposed to gradient concentrations of cisplatin (DDP) was detected by Western blotting with or without small interfering RNA (siRNA)-mediated Stat1 gene silencing. The effect of Sata1 silencing on the sensitivity to DDP and cell proliferation of the cells was tested using MTT assay and BrdU assay, and the expression of c-Myc was detected by Western blotting in the cells treated with siRNA and DDP. Results The expression of Stat1 in Hela cells exposed to DDP increased with the DDP concentrations, reaching 1.5 folds of the baseline at a DDP concentration of 5 mg/L and 2 folds at 10 mg/L. Stat1-siRNA effectively reduced Stat1 expression in Hela cells, promoted the cell proliferation, and enhanced the expression of c-Myc;DDP inhibited the cell growth and down-regulated c-Myc expression. Stat1-siRNA rescued DDP-induced inhibition of cell growth and c-Myc down-regulation. Conclusion The expression of Stat1 is associated with DDP sensitivity in cervical cancer cells, and Stat1 silencing can increase the sensitivity to DDP and c-Myc expression of the cells.