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

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

It was a single-center cross-sectional study to investigate the association of serum C3 level with blood pressure and estimated glomerular filtration rate (eGFR) in patients with idiopathic membranous nephropathy (IMN). The clinical and pathological data of 98 patients with IMN diagnosed by renal biopsy in the Department of Nephrology of East Hospital Affiliated to Tongji University from August 1, 2018 to October 31, 2023 were retrospectively analyzed. The demographic characteristics, serum complement C3 and other clinical data were compared between the non-hypertension group ( n=37) and hypertension group ( n=61). Pearson or Spearman correlation analysis method was used to analyze the correlation between serum C3 and eGFR in IMN patients and IMN patients with hypertension. Multiple linear regression analysis was used to analyze the related factors of eGFR in IMN patients with chronic kidney disease stage 1-3 in hypertension group. The results showed that compared with the non-hypertension group, the patients in hypertension group were older, and had higher levels of serum creatinine, cystatin C, urinary microalbumin to creatinine ratio, serum C3 and C4, and lower eGFR (all P<0.05). The correlation analysis showed that there was no correlation between serum C3 level and eGFR in IMN patients ( r=0.118, P=0.247). However, serum C3 level was positively correlated with eGFR in IMN patients with hypertension ( r=0.325, P=0.011). Multiple linear regression analysis showed that eGFR was negatively correlated with age ( β=-0.328, P=0.013), and positively correlated with serum C3 level ( β=0.228, P=0.048). The study shows that serum C3 level in hypertension group is higher than that in non-hypertension group in IMN patients. Moreover, serum C3 is positively correlated with eGFR.

Objective:To assess the clinical effect and safety of comprehensive therapy of traditional Chinese medicine(TCM)in the treatment of erectile dysfunction(ED)with damp-heat stasis.Methods:We selected 108 cases of ED with damp-heat stasis meeting the inclusion criteria and treated with tadalafil(the control group,n=54)or tadalafil+comprehensive TCM therapy(the trial group,n=54)in the First Affiliated Hospital of Henan University of Chinese Medicine in the same period.After 8 weeks of treatment,we recorded the patients'scores on IIEF-5,TCM syndrome,erectile quality(EQS),9-Item Patient Health Questionnaire(PHQ-9)and Generalized Anxiety Scale 7(GAD-7).At 16 weeks of our study,we collected the efficacy parameters,safety indicators and adverse reactions by telephone follow-up and compared the data obtained between the two groups of patients.Results:Totally,103 of the patients completed the study,51 in the control and 52 in the trial group.Compared with the baseline,the IIEF-5 and EQS scores were both markedly increased after 8 weeks of treatment in the trial group(12.35±3.00 vs 18.36±2.82,P＜0.05;39.5[30.25-43]vs 67.5[54.5-76.75],P＜0.05)and the control(11.96±2.79 vs 15.88±3.86,P＜0.05;38.0[29-42]vs 56[49-64],P＜0.05),even more significantly in the former than in the latter(P＜0.05);the TCM syndrome and GAD-7 scores were remarkably decreased in the trial(9.5[8-12]vs 4.0[2.25-5],P＜0.05;5[2.25-6.75]vs 2.5[1-4.75],P＜0.05)and the control group(10.0[8-12]vs 5.0[3-6],P＜0.05;5.0[3-6]vs 4.0[2-5],P＜0.05),even more signif-icantly in the former than in the latter(P＜0.05),so were the PHQ-9 scores(P＜0.05),but with no statistically significant differ-ence between the two groups(P＞0.05).The IIEF-5 scores of the two groups remained significantly higher than the baseline during the follow-up(P＜0.05),even higher in the trial than in the control group(17.04±2.60 vs 14.16±3.34,P＜0.05).No obvious abnormal safety indicators or adverse events were observed during the study.Conclusion:Comprehensive TCM therapy combined with tadalafil is superior to tadalafil alone in the treatment of ED with damp-heat stasis,and has a better long-term efficacy and a higher safety.

Objective To investigate the effect of endoscopic prebiopsy forceps on the detection rate of polyps in the right semicolon.Method Clinical data of 148 patients diagnosed and treated from March 2022 to December 2022 who were detected as polyps in the right semicolon by general electronic colonoscopy were collected,and clinical data of the patients who underwent endoscopic prebiopsy forceps were re-examined and the patients underwent endoscopic treatment within 1 month.The differences in general data,polyp number detected,polyp size,morphology and pathological diagnosis between the two groups were analyzed and compared.Results 168 polyps were detected in the right semicolon in the general colonoscopy group,and 41 polyps were missed in reexamination using endoscopic prebiopsy forceps,with a missed diagnosis rate of 19.62%.The detection rate of<5 mm polyps was higher in the endoscopic prebiopsy forceps group than that of general colonoscopy group,the difference was statistically significant(P<0.05).The polyps in the two groups were mainly wide-basal type,and the pathological properties were mainly tubular adenoma,there was no statistical significance among all groups(P>0.05).No complications such as bleeding and perforation occurred in the two groups.Conclusion Endoscopic prebiopsy forceps can significantly improve the detection rate of polyps in the right semicolon,in particular,the intraoperative search for disappeared preoperatively identified intestinal polyps,as well as smaller diameter intestinal polyps,which is worthy of further clinical promotion.

Mongolian medicine external treatment,which called five kinds of treatment in ancient time,is a kind of exter-nal treatment including fire moxibustion,poultice,soaking and other therapies.The therapy was gradually developed and per-fected in the course of Mongolian people's long-term struggle against diseases,which has characteristics of small trauma and suitable for long-term application.In this paper,the research progress of external treatment of orthopedic diseases in Mongolian medicine in recent years was summarized,and it was concluded that external treatment of orthopedic diseases in Mongolian medicine had distinct characteristics and accurate efficacy.However,there are still deficiencies in the standardization of clini-cal operation and the study of the mechanism of therapeutic action,which need further research and improvement.

Objective To compare the efficacies of acellular dermal matrix(ADM)and pedicle buccal fat pad flap(PBFPF)in repairing buccal soft tissue defect.Methods A total of 84 patients undergoing repair of buccal mucosa defect in our hospital were selected and randomly divided into the ADM group and PBFPF group,with 42 cases in each group.Patients of the ADM group were repaired tby ADM,while patients of the the PBFPF group were repaired by PBFPF.The repair time,oral feeding time,hospital stay were compared between the two groups.The maximum opening degree of patients before surgery,and 1 week,1 month and 6 months after surgery was measured and compared.The effective rate of repair and the occurrence of complications of patients were recorded.The improvement of oral and maxillofa-cial function(including swallowing function,language function and masticatory function)after surgery of patients were observed.Results There was no significant difference in the repair time,oral feeding time,hospital stay,total incidence of complications,postoperative swallowing function or postoperative language function between the two groups(P＞0.05).The maximum opening degree had no significant difference between the ADM group and PBFPF group or in the interaction effect between groups and time points(P＞0.05),but had signifi-cant difference in the comparison of time points(P＜0.05).The effective rate of repair for patients with defect area of＞13～20 cm2 in the PBFPF group was higher than that in the ADM group(P＜0.05).The masticatory function of patients in the PBFPF group was better than that in the ADM group(P＜0.05).Conclusion Both PBFPF and ADM have advantages in the repair of oral mucosal tissue defects,and PBFPF has better repair effect in patients with larger mucosal defect area(＞13～20 cm2).