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*

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To study the effects of Chrysanthemum Flos on blood pressure of spontaneously hypertensive rats(SHR)and evaluate its antioxidant activity in vitro and in vivo.Methods SHR were randomly divided into model,control and experimental-L,-H groups with 10 rats per group,and 10 WKY rats as blank group.Experimental-H,-L groups were given 2.10 and 0.525 g·kg-1 Chrysanthemum Flos extract by gavage;control group received 5.25 mg·kg-1 losartan by gavage;blank and model groups were given the same volume of 0.9％NaCl solution by gavage.Rats in each group were gavaged once a day for 8 weeks.After 8 weeks of continuous intragastric administration,the systolic blood pressure(SBP)and diastolic blood pressure(DBP)were observed.The contents of catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH)and malondialdehyde(MDA)in serum were measured with kit colorimetry method.The in vitro free radical scavenging rates of Chrysanthemum Flos extract were detected by 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2'-amino-di(2-ethyl-benzothiazoline sulphonic acid-6)ammonium salt(ABTS)methods.Results The SBP of blank,model,control and experimental-H,-L groups were(132.00±2.45),(204.00±4.55),(171.00±2.16),(181.00±3.74)and(184.67±4.78)mmHg;the DBP were(73.33±4.03),(175.67±3.40),(120.33±0.94),(125.33±2.87)and(125.67±2.36)mmHg;the contents of serum CAT were(9.24±3.99),(8.40±2.98),(9.24±2.42),(8.59±2.70)and(8.49±1.47)U·mL-1;the contents of serum SOD were(122.40±12.30),(75.30±28.37),(125.39±31.35),(110.92±26.14)and(103.37±22.31)U·mL-1;the contents of serum GSH were(117.93±10.18),(78.29±23.68),(118.57±26.08),(109.89±20.52)and(98.73±14.71)U·mL-1;the contents of serum MDA were(8.36±2.08),(8.45±3.38),(8.22±3.04),(7.09±3.21)and(7.24±3.32)nmol·L 1,respectively.Compared with model group,the differences of above indicators in control group and experimental-H,-L groups were statistically significant(P＜0.05,P＜0.01).Chrysanthemum Flos extract showed certain free radical scavenging ability in vitro.The highest scavenging rates of DPPH and ABTS were 90.29％and 92.67％,respectively.Conclusion Chrysanthemum Flos extract had good antihypertensive activity.The antioxidation ability might be its antihypertensive mechanisms.

Objective To investigate the diagnosis value of contrast-enhanced ultrasound (CEUS) in the differentiation of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) of the liver with ≤3 cm of maximum diameter. Methods The image characteristics in 48 lesions of HCC with maximum diameter≤3 cm and 48 lesions of FNH with maximum diameter≤3 cm confirmed by pathology were retrospectively analyzed. The phase changes, enhancement patterns and enhancement characteristics of the lesions in the two groups were compared. Results All lesions in the two groups showed high-echo in the arterial phase. The contrast arrival time in HCC group and FNH group was 17(15, 19) s and 15(12, 18.75) s (P＝0.017); the peak time in the two groups was 21(17, 25) s and 22(19, 26) s (P＞0.05). The main enhancement patterns of HCC group and FNH group in arterial phase were homogeneous enhancement and centrifugal enhancement, respectively. All HCC lesions showed homogeneous enhancement, which was significantly higher than FNH (2.08%, P＜0.05); 97.91% of FHN lesions showed centrifugal enhancement, which was higher that of HCC lesions (0, P＜0.05). During the CEUS process, 87.5% of HCC lesions showed “rapid fill-in and rapid wash-out”, which was significantly higher than that of FNH lesions（8.33%，P＜0.05）; 91.67% of FNH lesions showed “rapid fill-in” and “synchronous/slow wash-out” which was significantly higher than that of HCC lesions （12.50%，P＜0.05）. Conclusion CEUS is helpful in the differential diagnosis of FNH and HCC with maximum diameter≤3 cm．

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 investigate the expression level of HNRNP A1 in colorectal cancer(CRC)and its prognostic implications.Methods We investigated HNRNP A1 expression level in CRC using HPA,TIMER,and GEPIA databases and analyzed its association with Ki-67 and VEGFA expressions.Kaplan-Meier Plotter database was used to analyze the correlation of HNRNP A1 mRNA levels with the survival rates of CRC patients.Pathway enrichment analysis was performed for predicting the biological roles of HNRNP A1 in CRC progression.Immunohistochemistry and Western blotting were used to examine the protein levels of HNRNP A1 in CRC versus adjacent tissues,and TIMER was used for assessing its expression in the infiltrating immune cells.In RKO/Caco2 cells,the effects of lentivirus-mediated knockdown of HNRNP A1 on cell proliferation and migration were observed,and the inhibitory effect of VPC-80051(a HNRNP A1 inhibitor)on cell proliferation was evaluated to assess its potential as a therapeutic agent.Results HNRNP A1 was significantly overexpressed in CRC tissues and correlated with a poor prognosis of the patients.HNRNP A1 expression level was correlated with the infiltrating immune cells in CRC microenvironment and positively correlated with MKI67 and VEGFA expressions in CRC.A high HNRNP A1 expression predicted a in survival and progression-free survival of CRC patients and was involved in multiple biological processes related with CRC progression.In RKO/Caco2 cells,HNRNP A1 knockdown significantly suppressed cell proliferation and migration,and treatment with VPC-80051 also effectively inhibited CRC cell proliferation.Immunohistochemical study demonstrated a close correlation of HNRNP A1 overexpression with tumor stage of CRC.Conclusion HNRNP A1 is overexpressed in CRC tissues to modulate cell proliferation and migration and is correlated with a poorer prognosis.VPC-80051 can effectively inhibit CRC cell proliferation,suggesting the potential of HNRNP A1 as a therapeutic target for CRC.