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*

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Objective To explore the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for sedation in elderly patients undergoing ultrasound-guided transperineal prostate biopsy.Methods Forty-nine elderly male patients,aged 65-75 years,BMI 18.5-30.0 kg/m2,ASA physical stutas Ⅰ-Ⅲ,who underwent ultrasound-guided transperineal prostate biopsy,were randomly as-signed into the esketamine-ciprofol group(group E,n=23)and the ciprofol group(group C,n=26).After intravenous administration of sufentanil 0.1 μg/kg,patients in group E received esketamine 0.2 mg/kg,while patients in group C received the same volume of normal saline.The up-and-down sequential allocation method was used to calculate the effective dose of ciprofol.The initial dose of ciprofol was 0.2 mg/kg in group E and 0.3 mg/kg in group C,and the dose gradient was 0.05 mg/kg for both groups.If there was no body movement during the first puncture of prostate after the loss of eyelash reflex,the ciprofol dose in the next patient was reduced by 0.05 mg/kg.Otherwise,the ciprofol dose in the next patient was in-creased by 0.05 mg/kg.The study was completed until 7 inflection points alternating between non-body movement and body movement achieved.The total amount of ciprofol,surgical time,recovery time,stay in recovery room,hypotension,bradycardia,respiratory depression,injection pain,nausea and vomiting,and adverse reaction of the mental system were recorded.The Probit method was used to calculate the ED50 and 95%effective dose(ED95)with 95%confidence interval(CI)of ciprofol for inhibition of body movement.Results Compared with group C,the total amount of ciprofol in group E was significantly reduced(P＜0.05).There were no significant differences between the two groups in surgical time,recovery time,stay in recovery room,and adverse events.The ED50 of ciprofol in group E was 0.22 mg/kg(95%CI 0.19-0.26 mg/kg),and the ED50 in group C was 0.38 mg/kg(95%CI 0.31-0.46 mg/kg).Compared with group C,the ED50 in group E was significantly reduced(P＜0.05).The ED95 of ciprofol in group E was 0.28 mg/kg(95%CI 0.25-0.49 mg/kg),and the ED95 in group C was 0.51 mg/kg(95%CI 0.44-1.25 mg/kg).Compared with group C,the ED95 in group E was significantly reduced(P＜0.05).Conclusion The ED50 of ciprofol for inhibition of body movement in elderly patients undergoing ultrasound-guided transperi-neal prostate biopsy was 0.38 mg/kg,which was reduced to 0.22 mg/kg by using lose-dose esketamine 0.2 mg/kg as an adjuvant.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

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.

Objective To evaluate the myocardial microcirculation function of patients with acute myocardial infarction(AMI)after treatment with myocardial contrast-enhanced ultrasound combined with albumin(ALB)and lipoprotein a[Lp(a)].Methods Ninety-six patients with AMI admitted to our hospital from January 2022 to September 2023 were selected.According to myocardial microcirculation function after treatment,they were divided into a normal function group(56 cases)and a dysfunction group(40 cases).major cardiovascular adverse events were compared between the two groups.major cardiovascular adverse events(MACE),the plateau peak intensity of myocardial contrast ultrasound parameters(A value),the rise rate of microbubble reperfusion(β value),myocardial blood flow(A value×β value),and serum ALB and Lp(a)levels after 48h of treatment were different,so as to determine the evaluation value of myocardial contrast ultrasound,ALB and Lp(a)on myocardial microcirculation function in AMI patients after treatment.Results In the dysfunction group,the parameters A,β,A×β,and serum ALB level,Lp(a)was higher than that in the normal function group(P＜0.05).A,β,A×β,ALB were positively correlated with cardiac function,and Lp(a)was negatively correlated with cardiac function(P＜0.05).CEUS combined with ALB and Lp(a)evaluated the efficacy of myocardial microcirculation in patients with AMI(P＜0.05).The incidence of MACE was higher in the functional group than in the normal functional group(P＜0.05).Conclusion Myocardial contrast-enhanced ultrasound can early evaluate the myocardial microcirculation function in patients with acute myocardial infarction after treatment,and combined with serum ALB and Lp(a),it can improve diagnostic efficacy.