Objective To investigate the effects of galangin on the proliferation,apoptosis,and 5-fluorouracil (5-FU) resistance of colorectal cancer (CRC) cells by regulating the FOXO3-FOXM1 axis. Methods CRC cells HCT8 and its drug-resistant cell lines HCT8/5-FU were cultured in vitro,and then treated with different concentrations (0,5,10,20,40 μmol/L) of galangin to screen experimental concentra-tions. HCT8 cells were divided into the ctrl group (without special treatment),NC group (transfected with empty plasmid),L-galangin group (treated with 10 μmol/L of galangin ),H-galangin group (treated with 20 μmol/L of galangin),and H-galangin+sh-FOXO3 group (trans-fected with FOXO3 shRNA plasmid after 20 μmol/L of galangin treatment). HCT8/5-FU cells were divided into the control group (without special treatment),5-FU+NC group (treated with empty plasmid after 5 μg/mL of 5-FU treatment),5-FU group (treated with 5 μg/mL of 5-FU),5-FU+L-galangin group (treated with 10 μmol/L of galangin after 5 μg/mL of 5-FU treatment),5-FU+H-galangin group (transfected with 20 μmol/L galangin after 5 μg/mL of 5-FU treatment),and 5-FU+H-galangin+sh-FOXO3 group (transfected with FOXO3 shRNA plasmid after 5 μg/mL of 5-FU and 20 μmol/L of galangin treatment). The cell proliferation ability was detected by CCK-8 assay;the cell clone formation ability was detected by clone formation assay;the cell apoptosis was detected by flow cytometry;the expression of related proteins were detected by Western blot.Results In HCT8 cells,compared with 0 μmol/L of galangin treatment,10,20,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). In HCT8/5-FU cells,compared with 0 μmol/L galangin treatment,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). After 10 and 20 μmol/L of galangin treatment,the apoptosis rate,and the expression of FOXO3 and Bax proteins were increased (P<0.05),while cell survival rate,clone formation number,and expression of FOXM1 and PCNA proteins decreased in HCT8 and HCT8/5-FU cells (P<0.05),and the MRP-1 protein expression in HCT8/5-FU cells decreased (P<0.05). Knocking down sh-FOXO3 could attenuate the effects of high dose of galangin on HCT8 and HCT8/5-FU cells (P<0.05). Conclusion Galangin may inhibit the proliferation,promote apoptosis,and reduce 5-FU resistance of CRC cells by regulating the FOXO3-FOXM1 axis.

Nodal marginal zone B-cell lymphoma(NMZL),the least common subtype of marginal zone lymphoma,represents a low-grade malignancy arising from the marginal zone of lymph node follicles,composed of small B-cells with an inert non-Hodgkin lymphoma nature.It accounts for 1.5% to 1.8% of all non-Hodgkin lymphomas and 10% of all marginal zone lymphomas.The low incidence and lack of typical clinical and pathological features pose a challenge to the diagnosis and clinical management of NMZL.In this article,we reported the diagnosis and treatment of a case of NMZL located in the parapharyngeal space of the left neck and reviewed the relevant literature from both domestic and international sources.We summarized the clinical manifestations,histopathological features,immunohistochemical characteristics,imaging features,diagnosis and treatment modalities,and prognosis of NMZL.
Humans ; Lymphoma, B-Cell, Marginal Zone/pathology* ; Lymph Nodes/pathology* ; Neck/pathology* ; Male

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

BACKGROUND:Ankle inversion injuries frequently occur during landing,injuring the anterior talofibular and calcaneofibular ligaments.Previous studies usually used indirect indicators,such as inversion angle,as an injury risk indicator,but epidemiological support is lacking.OBJECTIVE:To calculate anterior talofibular and calcaneofibular ligament strains using a three-dimensional multi-body foot model during a drop-landing and to investigate whether increasing the foot toe-out angle for landing would reduce the risk of inversion sprains.METHODS:Thirty-five participants with high sports demands[15 males and 20 females,age:(21.0±0.9)years,height:(176.2±8.8)cm,body mass:(71.6±12.8)kg]were recruited to perform a drop-landing test using a trapdoor device to simulate ankle inversion sprains.Two landing conditions were tested,i.e.,natural landing and toe-out landing.Kinematic data were collected using a 12-camera motion analysis system,the strains of the anterior talofibular and calcaneofibular ligaments were calculated using a three-dimensional rigid-body foot model.RESULTS AND CONCLUSION:From natural landing to toe-out landing conditions,the anterior talofibular ligament strain decreased[natural landing=(3.57±1.92)％,toe-out landing=(0.36±1.18)％,P＜0.001,Cohen's d=2.01),as was the calcaneofibular ligament strain[natural landing=(1.38±1.80)％,toe-out landing=(0.28±2.29)％,P=0.003,Cohen's d=0.81).It could be concluded that increasing foot toe-out angle reduces anterior talofibular and calcaneofibular ligament strains during drop-landing with ankle inversion,thereby reducing the potential of ankle inversion sprains.

Objective:To investigate the clinical features and prognostic factors of primary tonsil lymphoma(PTL).Methods:The clinical data of 41 patients diagnosed with PTL and treated in the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2022 were collected and retrospectively analyzed.Their clinical features and prognostic factors were analyzed.Results:All the 41 patients were newly diagnosed with PTL,and the median age of onset was 58(19-85)years.Among them,19 patients started with pharyngeal pain,12 patients presented with dysphagia,8 patients presented with pharyngeal mass,and 2 patients presented with blurred articulation.The most common pathological type was diffuse large B-cell lymphoma(24 cases,58.54％).All patients received chemotherapy,and 3 patients were combined with hematopoietic stem cell transplantation.Among 41 patients,11(26.83％)achieved complete response,14(34.15％)achieved partial response,and the total response rate was 60.98％(25/41).The median follow-up time was 37(6-107)months,the 5-year overall survival(OS)rate was 70.81％and 5-year progression-free survival(PFS)rate was 66.20％.Univariate analysis showed that B symptoms,Ki-67,β2-MG and IPI score had significant effects on PFS and OS of patients(all P＜0.05).Multivariate analysis showed that IPI score was an independent risk factor for PFS and OS of patients(P＜0.05).Conclusion:The clinical manifestations of PTL lack specificity,and the prognosis is relatively good.Most patients can achieve long-term survival after treatment.IPI score is related to the prognosis.

Objective To investigate the effects of galangin on the proliferation,apoptosis,and 5-fluorouracil (5-FU) resistance of colorectal cancer (CRC) cells by regulating the FOXO3-FOXM1 axis. Methods CRC cells HCT8 and its drug-resistant cell lines HCT8/5-FU were cultured in vitro,and then treated with different concentrations (0,5,10,20,40 μmol/L) of galangin to screen experimental concentra-tions. HCT8 cells were divided into the ctrl group (without special treatment),NC group (transfected with empty plasmid),L-galangin group (treated with 10 μmol/L of galangin ),H-galangin group (treated with 20 μmol/L of galangin),and H-galangin+sh-FOXO3 group (trans-fected with FOXO3 shRNA plasmid after 20 μmol/L of galangin treatment). HCT8/5-FU cells were divided into the control group (without special treatment),5-FU+NC group (treated with empty plasmid after 5 μg/mL of 5-FU treatment),5-FU group (treated with 5 μg/mL of 5-FU),5-FU+L-galangin group (treated with 10 μmol/L of galangin after 5 μg/mL of 5-FU treatment),5-FU+H-galangin group (transfected with 20 μmol/L galangin after 5 μg/mL of 5-FU treatment),and 5-FU+H-galangin+sh-FOXO3 group (transfected with FOXO3 shRNA plasmid after 5 μg/mL of 5-FU and 20 μmol/L of galangin treatment). The cell proliferation ability was detected by CCK-8 assay;the cell clone formation ability was detected by clone formation assay;the cell apoptosis was detected by flow cytometry;the expression of related proteins were detected by Western blot.Results In HCT8 cells,compared with 0 μmol/L of galangin treatment,10,20,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). In HCT8/5-FU cells,compared with 0 μmol/L galangin treatment,40 μmol/L of galangin treatment decreased the cell survival rate (P<0.05). After 10 and 20 μmol/L of galangin treatment,the apoptosis rate,and the expression of FOXO3 and Bax proteins were increased (P<0.05),while cell survival rate,clone formation number,and expression of FOXM1 and PCNA proteins decreased in HCT8 and HCT8/5-FU cells (P<0.05),and the MRP-1 protein expression in HCT8/5-FU cells decreased (P<0.05). Knocking down sh-FOXO3 could attenuate the effects of high dose of galangin on HCT8 and HCT8/5-FU cells (P<0.05). Conclusion Galangin may inhibit the proliferation,promote apoptosis,and reduce 5-FU resistance of CRC cells by regulating the FOXO3-FOXM1 axis.

BACKGROUND:Ankle inversion injuries frequently occur during landing,injuring the anterior talofibular and calcaneofibular ligaments.Previous studies usually used indirect indicators,such as inversion angle,as an injury risk indicator,but epidemiological support is lacking.OBJECTIVE:To calculate anterior talofibular and calcaneofibular ligament strains using a three-dimensional multi-body foot model during a drop-landing and to investigate whether increasing the foot toe-out angle for landing would reduce the risk of inversion sprains.METHODS:Thirty-five participants with high sports demands[15 males and 20 females,age:(21.0±0.9)years,height:(176.2±8.8)cm,body mass:(71.6±12.8)kg]were recruited to perform a drop-landing test using a trapdoor device to simulate ankle inversion sprains.Two landing conditions were tested,i.e.,natural landing and toe-out landing.Kinematic data were collected using a 12-camera motion analysis system,the strains of the anterior talofibular and calcaneofibular ligaments were calculated using a three-dimensional rigid-body foot model.RESULTS AND CONCLUSION:From natural landing to toe-out landing conditions,the anterior talofibular ligament strain decreased[natural landing=(3.57±1.92)％,toe-out landing=(0.36±1.18)％,P＜0.001,Cohen's d=2.01),as was the calcaneofibular ligament strain[natural landing=(1.38±1.80)％,toe-out landing=(0.28±2.29)％,P=0.003,Cohen's d=0.81).It could be concluded that increasing foot toe-out angle reduces anterior talofibular and calcaneofibular ligament strains during drop-landing with ankle inversion,thereby reducing the potential of ankle inversion sprains.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

OBJECTIVE To clarify the components of volatile oil in branches and leaves of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii. METHODS The total volatile oil in leaves and branches of these plants were obtained by supercritical CO2 extraction. After that, the chemical composition of the total volatile oil was analyzed and identified by GC-MS, and the contents of different parts and varieties were compared. RESULTS The results showed that the highest oil yield of leaves was Rhododendron thymifolium(6.97%), and the highest oil yield of branches was Rhododendron anthopogonoides(20.53%). Thirty-five, eighty, fifty-eight and forty compounds were detected in the branch oil of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii respectively, among which Rhododendron capitatum was rich in compounds. Forty-eight, fifty-seven, sixty-two and fifty compounds were detected in the leaf oil, among which the compounds of Rhododendron anthopogonoides were the richest. Among the detected components, squalene(34.92%, 26.90%) was the highest content in the branches and leaves of Rhododendron anthopogonoides. 1-Eicosanol(26.79%) was the highest content in the branch oil of Rhododendron capitatum, and octadecyl acetate(42.32%) was the highest content in the leaf oil. The highest content of bisabola-3,10-diene-2-one(34.66%, 28.20%) was found in the branches and leaves of Rhododendron thymifolium, and 15-oxoETE(38.20%, 40.40%) was the highest content in the branches and leaves of Rhododendron przewalskii. The results showed that the contents of oil in branches and leaves of Rhododendron capitatum were quite different in different parts. In the comparison of different varieties, the compounds with the highest content of four rhododendrons were all different. CONCLUSION According to the difference of the content of active components of different rhododendrons and parts, the appropriate species and parts for purposeful development and utilization should be selected. The research results can provide scientific basis for rational development and utilization of Rhododendron resources.