OBJECTIVE To systematically evaluate the efficacy and safety of different chemotherapy combination regimens for first-line treatment of metastatic colorectal cancer （mCRC）. METHODS PubMed， Cochrane Library， Embase and Web of Science were electronically searched to collect randomized controlled clinical trial （RCT） on first-line treatment for mCRC from January 1， 2000 to February 16， 2025. Two reviewers independently screened literature， extracted data and assessed the risk of bias of the included studies. Network meta-analysis was performed by using R4.4.3 and Stata 17.0 software. RESULTS A total of 28 RCTs， involving 16 intervention measures， were included. In terms of prolonging progression-free survival （PFS） and overall survival （OS）， FOLFOX （5-fluorouracil+oxaliplatin+calcium folinate regimen）+cetuximab had the highest probability of ranking first. In terms of improving objective response rate （ORR）， FOLFOXIRI （5-fluorouracil+oxaliplatin+irinotecan+calcium folinate regimen）+ bevacizumab and FOLFOX+bevacizumab+nivolumab had the highest probability of ranking first； in terms of the incidence of grade 3 or higher adverse reactions， FOLFOXIRI+panitumumab had the highest probability of ranking first； in subgroup analysis of KRAS wild-type patients， FOLFIRI （5-fluorouracil+irinotecan+calcium folinate regimen）+panitumumab and FOLFIRI+bevacizumab had the highest probability of ranking first in terms of prolonging PFS and OS， respectively； in terms of ORR， FOLFOXIRI+ cetuximab had the highest probability of ranking first. CONCLUSIONS In first-line treatment for mCRC， FOLFOX combined with targeted therapy has advantages in terms of efficacy and safety. However， individualized treatment strategies should be formulated based on the KRAS gene status and tumor location of patients.

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

OBJECTIVE: To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first. RESULTS: Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% ［39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)］. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy. CONCLUSION The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Cytarabine/administration & dosage* ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Retrospective Studies ; Male ; Female ; Decitabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anthracyclines/administration & dosage* ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Recurrence

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

Postoperative nausea and vomiting (PONV) are common complications that mainly occur within 24 h after orthognathic surgery. The incidence of nausea and vomiting after orthognathic surgery remains high and is a difficult problem for patients and surgeons. These complications not only affect wound healing and increase the risk of postoperative bleeding. Vomit and blood may also cause nausea and vomiting, which results in a vicious cycle. Frequent nausea and vomiting are a painful experience and more serious than postoperative pain. They are one of the main reasons for postoperative infection, delayed discharge, and increased hospitalization costs and affect patient satisfaction. In this review, the author combined literature review and clinical experience and summarized and analyzed the causes of orthognathic nausea and vomiting and prevention and treatment strategies to improving the related clinical process.
Humans ; Postoperative Nausea and Vomiting/etiology* ; Orthognathic Surgical Procedures/adverse effects*

Aim To explore the effects of sirolimus on the growth and development of motor,vascular,nerv-ous,and immune systems through zebrafish models.Methods After 3 hours of fertilization of zebrafish embryos,different concentrations of sirolimus were add-ed to the growth environment,and the growth and de-velopment of the embryos was recorded.Transgenic ze-brafish models labeled with blood vessels,nerves or im-mune cells were used to compare the drug effects on the growth and development of those systems.Results At the concentration of 0.5 μmol·L-1,the hatching rate and the body length(P＜0.01)were significantly smaller than those of the control group,and movement was also significantly slowed down.Meanwhile,the length of axons of the nervous system,the development of intersegmental vessels,and the growth of immune cells were significantly delayed by drug treatment.But when the concentration was below 0.1 μmol·L-1,there was no statistically difference between the control group and the sirolimus group.Conclusions When the concentration of sirolimus exceeds a certain level,it can significantly slow down the growth and development of movement,blood vessels,nervous system and im-mune system of zebrafish.Therefore,in clinical prac-tice,it is important to monitor the blood concentration of sirolimus in children on time.

Objective To evaluate the dose distribution and execution accuracy of intensity-modulated radiation therapy(IMRT)plans with different minimum segment widths for patients with primary liver cancer,thereby providing reference for the radiotherapy planning.Methods A retrospective study was conducted on 30 patients with primary liver cancer.With the other optimization condition unchanged,5 IMRT plans with minimum segment widths of 0.6,0.8,1.0,1.2 and 1.5 cm were made for each patient,and the dose distribution,execution efficiency and gamma passing rate of the 5 plans were compared.Results The monitor units and delivery time of the 5 plans decreased with increasing minimum segment width,while the gamma passing rates at 3 mm/3%and 2 mm/2%tended to increase,with statistical differences(P<0.05).Conclusion The 5 plans in the study can be used for clinical treatment.While meeting the clinical requirements,reasonably setting the minimum segment width in IMRT plan can reduce monitor units,shorten delivery time,and improve treatment accuracy.

Objective:To assess the predictive value of a combined multiclassification model for computed tomography(CT)in the patholo-gical analysis of ground-glass nodules(GGN).Methods:Pulmonary GGN lesions that were pathologically confirmed as invasive adenocar-cinoma(IAC),minimally invasive adenocarcinoma(MIA),adenocarcinoma in situ(AIS),and preinvasive lesions(PILs),were collected from pa-tients who were treated at The First Affiliated Hospital of Xinxiang Medical University between February 2019 and March 2023.A total of 324 nodules were retrospectively collected from 285 patients,and divided into three groups:infiltrating IAC,MIA,and PILs.Radiomics and clinical-CT features were selected through recursive feature elimination and univariate Logistic regression.Seven models were constructed using Logistic regression(LR),support vector machine(SVM),random forest(RF),and integrative learning(stacking).Results:The hybrid model combining clinical-CT-radiomics features and an integrative strategy showed superior predictive performance,with an accuracy of 0.791,precision of 0.788,specificity of 0.857,recall of 0.790,and F1-Score of 0.789.Conclusions:The multiclassification joint model based on CT-radiomics is effective in predicting pathological classification of pulmonary GGNs.This model aids in accurate imaging diagnosis and can provide a basis for optimizing treatment plans.

Objective To analyze the expression of N-MYC and N-MYC downstream regulated gene-1(NDRG1)in gastric cancer tissues,and to assess their effects on biological characteristics of gastric cancer cells.Methods Paired of gastric cancer tissues and adjacent normal tissues resected from 82 cases of patholog-ically confirmed gastric cancer who underwent surgical treatment in the hospital from January 2021 to May 2023 were collected.Gastric cancer tissues and adjacent normal tissues of 82 patients who were surgically re-sected and pathologically diagnosed with gastric cancer in the hospital from January 2021 to May 2023 were collected.Real-time quantitative PCR(qPCR)was used to detect the relative mRNA expression levels of N-MYC and NDRG1,and clinical data of the patients were collected.The correlation between the mRNA expres-sion of N-MYC and NDRG1 and clinicopathological features of the patients was discussed.NCI-N87 cells in logarithmic growth phase were selected and cultured in vitro.N-MYC interference plasmid(si-N-MYC)and its negative control(si-NC)was transfected into NCI-N87 cells,respectively,which were recorded as si-NC group and si-N-MYC group.Moreover,si-N-MYC was co-transfected into NCI-N87 cells with anti-NC and an-ti-NDRG1,respectively,and denoted as si-N-MYC+anti-NC group and si-N-MYC+anti-NDRG1 group.CCK-8 assay was used to detect cell proliferation activity,Transwell assay was used to detect cell invasion ability,and Western blotting assay was used to detect N-MYC and NDRG1 protein expression in cells.Results The relative expression of N-MYC mRNA in gastric cancer tissues was higher than that in paracancer tissues(P＜0.05),and the relative expression of NDRG1 mRNA was lower than that in paracancer tissues(P＜0.05).There were significant differences in the expression of N-MYC and NDRG1 mRNA in patients with different TNM stages,lymph node metastasis and distant metastasis(P＜0.05).Compared with the si-NC group,the cell proliferation and invasion ability of the si-N-MYC group were decreased(P＜0.05),and the expression of NDRG1 protein was down-regulated(P＜0.05).Compared with si-N-MYC+anti-NC group,cell proliferation and invasion ability of si-N-MYC+anti-NDRG1 group were increased(P＜0.05).N-MYC could target and regulate NDRG1,and knocking down NDRG1 could reverse the biological effects of N-MYC on gastric cells.Conclusion In gastric cancer tissue,N-MYC mRNA expression is upregulated and NDRG1 mRNA expression is downregulated,both of which play important roles in the regulation of malignant biological behaviors such as proliferation and invasion of gastric cancer cells.

Tinnitus is a clinically refractory disease with a high incidence.LAI's Tongyuan acupuncture method believes that tinnitus is nothing more than the two ends of deficiency and excess.The deficiency is closely related to original spirit,and the excess is related to the pathological factors such as externally-contracted six pathogenic factors,phlegm-damp and blood stasis,and qi stagnation and yang constraint.The Tongyuan acupuncture method is based on original spirit,takes the two vessels of conception vessel(CV)and governor vessel(GV)as the general outline,takes the regulation of yin and yang as the main method,pays attention to the combination of local and overall,and emphasizes the application of tonification and purgation,and has the clinical effect of reinforcing healthy qi and dispelling pathogen,cultivating the vital essence.In clinical application,the method of'unblocking governor vessel and nourishing spirit'is used to play the role of heart and brain nourishing spirit and warming and supporting yang qi.The method of'conducting qi back to its source'has the effect of cultivating the vital essence and regulating qi movement.The treatments should be cooperated according to the syndromes,so that the pathogens can be expelled and healthy qi can be settled.Qi and blood have origins of generation and transformation and normally nourishing in the ear,so as to effectively alleviate the patient's tinnitus symptoms.This paper summarizes and analyzes Professor LAI Xin-Sheng's Experience in the diagnosis and treatment of tinnitus by Tongyuan acupuncture method,and provides a new acupuncture treatment plan for clinical application.