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 compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Lung cancer has the highest morbidity and mortality among malignant tumors worldwidely. Targeted therapy related to non-small cell lung cancer (NSCLC) is the research hotspot in recent year. The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has brought a huge change in the treatment of patients with EGFR mutation. The patients with EGFR exon20 insertion are specific cohort in NSCLC. Reviewing the clinical researches to EGFR exon20 insertion mutation positive NSCLC, as well as summarizing character, testing methods and treatment, will provide a help for clinical application, bringing more benefits for patients at the same time.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Background and purpose:Checkpiont targeted immunotherapy in the field of solid tumor therapy has huge potential, triggering a boom in the study of immune targeted drugs. A study has provided a basis for the follow-up study of ipilimumab combined with chemotherapy in the treatment of non-small cell lung cancer(NSCLC) patients. This study counted the adverse event statistics that ipilimumab or placebo combined with paclitaxel and carboplatin as first-line therapy for the treatment of stage Ⅳ or recurrent squamous cell carcinoma to evaluate the safety of ipilimumab combined with chemotherapy in the treatment of advanced squamous cell carcinoma.Methods:This study selected 13 patients with ECOG scores≤1 and stage ⅣA or ⅣB squamous cell carcinoma in the Shanghai Chest Hospital, Shanghai Jiao Tong Uni-versity. Randomized controlled double blind trial was used in this study. The patients of experimental group were treated with ipilimumab combined with paclitaxel and carboplatin, while the patients of control group were treated with the placebo combined with paclitaxel and carboplatin. Adverse events (AEs) were counted in the process of treatment.Results:The most common AEs were the 1/2 grade AEs. Immune-related AEs (irAEs) reported in the ipilimumab group included level Ⅰ of diarrhea and pruritus, level Ⅱ of rash and pruritus and level Ⅲ of hypophysitis.Conclusion:The side effects of ipilimumab were mild, tolerable and manageable.

Objective: To analyze the clinical, pathological and radiological characteristics of paragonimiasis in children for accurate diagnosis and therapy. Methods: A total of 31 patients with paragonimiasis treated from 2002 to 2016 were selected, including 17 cases from migrant areas and 14 cases from Wenzhou area. Results: In migrant children group, the serum IgE was significantly higher than that in Wenzhou area group [(2 379±944) IU/mL∶(1 552±1 121) IU/mL, t=-2.23, P<0.05], and the duration of therapy was remarkable longer [(13.8±6.5) days∶(9.9±3.4) days, t=-2.15, P<0.05]. Among all cases, 10 showed polyserositis including pleural effusion, ascites and pericardial effusion at different degrees on chest CT scans. Five cases with cerebral paragonimiasis were confirmed by MR imaging. Most of the lesions were located in the parietal lobe with slight low signal on T1WI but high signal on T2WI surrounded by disproportionate edema. Annular enhancement was prominent by Gd-DTPA. Paragonimiasis serum antibody was positive in all cases by ELISA. Pathologic features included formation of irregular lacunae or sinus tracts, presence of paragonimus bodies, and eosinophilic infiltration in the adjacent tissues. Conclusions Clinical manifestations of paragonimiasis are complex and non-specific in children.In migrant children group, clinical manifestations are diverse, more serious with more complications and difficulties in treatment, while patients in Wenzhou area group have favorable prognosis and less complicated treatment. The early diagnosis and timely treatment should be determined by patient′s detailed history, eosinophilic count, radiologic findings and immunological test to avoid serious complications.

Objective To study the association of body mass index (BMI) and waist circumference (WC) with dyslipidemia and the risk of dyslipidemia at different BMI and WC level among adults in Suzhou Industrial Park District. Methods A total of 6219 participants were chosen by stratified random cluster sampling method. Four streets were selected form the district first, then one community as a cluster was selected randomly from each street. Questionnaire survey, physical examination and laboratory tests were done by all subjects. Results The prevalence of dyslipidemia was 35.9％;the rates of overweight, obesity and central obesity were 36.6％, 9.6％ and 49.5％ respectively. The prevalence of dyslipidemia in underweight group, normal weight group, overweight group and obesity group were 13.6％, 30.2％, 47.7％and 59.0％ for male, and 17.2％, 27.3％, 38.6％和 48.8％ for female respectively. The prevalence of dyslipidemia for male and female both rose with BMI (χ2=139.848, P<0.001; χ2=92.387, P<0.001). The prevalence of dyslipidemia in the high waist circumference group and normal group were 50.2％and 30.9％for male, and 40.8％and 23.8％for female respectively. Prevalence of groups with high waist circumference for male and female were significantly higher than normal groups (χ2=108.669, P<0.001; χ2=110.642, P<0.001). Pearson correlation analysis showed that total cholesterol (TC), triglyceride(TG), and low density lipoprotein cholesterol (LDL-C) were positively correlated with BMI ( r=0.153, P<0.001;r=0.227, P<0.001;r=0.192, P<0.001), and were also positively correlated with WC(r=0.138, P<0.001; r=0.234, P<0.001; r=0.159, P<0.001). High density lipoprotein cholesterol(HDL-C) was negatively correlated with BMI (r=-0.189, P<0.001) and WC (r=-0.185, P<0.001). Logistic regression analysis after age adjustment showed that, compared to the group with BMI<24 kg/m2 and WC<85 cm(male)/WC<85 cm (female), odds ratios (OR) for male in group with BMI<24 kg/m2 and WC≥85 cm, group with BMI≥24 kg/m2 and WC<85 cm and group with BMI≥24.0 kg/m2and WC≥85 cm were 1.602, 1.834 and 3.064 respectively, and ORs for female in group with BMI<24.0 kg/m2 and WC≥80 cm and group with BMI≥24.0 kg/m2 and WC≥80 cm were 1.703 and 2.381 respectively, however, the OR for female in group with BMI≥24.0 kg/m2 and WC<85 cm was not statistically significant (P>0.05). Conclusions BMI, waist circumference and dyslipidemia were closely correlated. Waist circumference is more important than BMI for female.

Objective:To explore the change of B cell numbers in active MRL/lpr lupus mice , and their regulation mechanisms.Methods:B cell cycle and the percent of B cells in spleen lymphocytes of active MRL /lpr lupus mice and normal C 57/B6 mice were analyzed by using flow cytometry .The apoptotic B cells and their subclass were analyzed by Annexin V and PI staining.Further more ,B cells were purified by magnetic sorting , and real-time quantitative PCR was carried out to detect apoptosis-related gene.Results:Compared with the C57/B6 mice,the percent of B cells in active MRL/lpr lupus mice were significantly reduced (P<0.01),while the percent of apoptotic cells were significantly increased (P<0.01).The percent of early apoptotic B cells were sig-nificantly increased ( P <0.01 ) which including the immature and mature B cells , while the late apoptotic B cells were unchanged.Further more,we found that the anti-apoptotic protein BIRC3 was significantly reduced in active lupus B cells (P<0.01), while the pro-apoptotic protein BCL2L1 and BBC3(PUMA) were significantly increased(P<0.01).Conclusion: B cells in active lupus mice were significantly reduced while early apoptotic B cells were increased , which may be attributed to the changed balance between the anti-apoptotic and pro-apoptotic proteins , suggesting the reduction of B cells in SLE patients may be related to their increased early apoptosis .

Objective:To explore the effect of histone demethylase JMJD3 on B cell activation and apoptosis.Methods:B cells were sorted and purified from the peripheral blood of healthy people and SLE patients by using magnetic bead.After B cells were treated with IFN-αor R848 or IFN-α+R848,the percentages of CD86+B cells,CD69+B cells,CD86+Annexin V+B cells and CD69+Annexin V+B cells were detected by flow cytometry.The expression of JMJD3 was detected by Real Time PCR and Western blot.Results:The purity of sorted B cells was up to 95%.IFN-αenhanced both the activation and apoptosis and the JMJD3 expression of TLR7-activated B cells.The expression of JMJD3 was dependent on MAPK signal pathway,but not the NF-κB signaling pathway.Moreover,JMJD3 was highly expressed in B cells of peripheral blood from SLE patients compared to those from healthy people.Furthermore,JMJD3 inhibitors could inhibit the activation and apoptosis of IFN-αand R848 activated B cells.Conclusion:JMJD3 participated in the activation and apoptosis of IFN-αand TLR7-induced B cells, suggesting JMJD3 inhibitors may possess therapeutic effect for alleviating symptom of SLE.