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*

The traditional Chinese medicine （TCM） in pediatric care has a long history，proven efficacy，and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases，enhancing diagnostic and treatment levels，inheriting TCM knowledge，promoting the integration of TCM and Western medicine，and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not，excelling at what others have，being special in what others excel at，and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems，including respiratory，digestive，endocrine，psychological，and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon，such as upper respiratory tract infections，coughs，pneumonia，allergic rhinitis，bronchial asthma，atopic dermatitis，functional dyspepsia，functional constipation，enuresis，marginal short stature，simple obesity，attention deficit hyperactivity disorder，and tic disorders.The overall advantages were reflected in three aspects：First，the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases，making the treatment methodical and precise.Second，most traditional Chinese herbs are natural and have strong safety profiles.Third，TCM treatment methods are abundant，especially the external treatment methods，which are widely used in pediatrics，highly accepted by parents，and have definite efficacy，as well as good safety and compliance.

【Objective】 To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. 【Methods】 The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. 【Results】 The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count<20×10⁹/L(P=0.020, OR1.543, 95%CI1.072-2.220), prior pregnancy(P=0.000, OR5.187, 95%CI3.689-7.293), transfusions before admission(P=0.001, OR1.762, 95%CI1.257-2.470)and total platelet transfusion volumes after admission≥30 U(P=0.000, OR2.352, 95%CI1.638-3.376). Age ≥30 years old(P=0.023, OR=1.839, 95%CI1.088-3.108)and prior pregnancy(P=0.042, OR=5.258, 95%CI1.062-26.038)are associated with the production of anti-HLA class Ⅰ and class Ⅱ antibodies, respectively. The time from disease diagnosis to antibody testing≥41 days(P=0.000, OR=2.873, 95%CI1.612-5.119), initial platelet count<20×10⁹/L(P=0.008, OR=2.164, 95%CI1.225-3.822), prior pregnancy(P=0.002, OR=6.734, 95%CI1.993-22.751), transfusions before admission(P=0.001, OR=2.746, 95%CI1.531-4.925)and total platelet transfusion volumes after admission>30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. 【Conclusion】 Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.

BACKGROUND:Unicompartmental knee arthroplasty can effectively treat severe unilateral knee osteoarthritis.It has been found that posterior tibial cortical fracture is prone to occur after unicompartmental knee arthroplasty.The fracture begins at the keel groove of tibial osteotomy.The tibial prosthesis riser length affects the biomechanical results of the knee joint after unicompartmental knee arthroplasty. OBJECTIVE:To investigate the effect of tibial prosthesis riser length on knee biomechanics in unicompartmental knee arthroplasty,and to find out the relationship between prosthesis riser length and anterior and posterior tibial diameters of patients. METHODS:Computed tomography image data and commonly used unicompartmental prostheses were selected from a 37-year-old healthy female with no history of knee disease.A natural knee joint model was established and a unicompartmental prosthesis model was built.Eight different lengths of tibial prosthesis risers were established,with a minimum length of 31 mm and a maximum length of 34.5 mm in 0.5 mm increments,for comparison with the commonly used hospital prosthesis riser length of 33.2 mm.The material of the femoral component and tibial disc was cobalt-chromium-molybdenum alloy,and the tibial spacer was ultra-high molecular weight polyethylene.The biomechanical changes of the knee joint were observed using finite element analysis software loaded with 1000 N over the femur. RESULTS AND CONCLUSION:(1)The tibial stress was minimal at a tibial prosthesis riser length of 33 mm;the anterior cruciate ligament stress was minimal;the lateral meniscus stress was minimal,and the femoral prosthesis stress was minimal.The remaining components were less stressful.(2)The subject's medial tibial plateau anterior-posterior diameter length was 53 mm,and by calculating the ratio,the optimal ratio of tibial prosthesis riser length to anterior-posterior tibial diameter should be about 62%.If it is lower than this value,aseptic loosening of the prosthesis may occur,and if it is higher than this value,fracture of the bone cortex at the anterior-posterior end of the tibia may occur.

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.