OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

Bladder cancer is one of the most prevalent cancers worldwide, with a high rate of recurrence and mortality, which is the ninth most common malignancy globally. Cystoscopy remains the gold standard for clinical bladder cancer diagnosis, but its invasive nature can lead to bacterial infection and inflammation. Urine cytology is a non-invasive and simple diagnostic method, but it has lower sensitivity in detecting low-grade bladder cancer and may yield false negative results. Therefore, identifying ideal diagnostic and prognostic biomarkers is crucial for accurate diagnosis and effective treatment of bladder cancer. Aptamers, characterized as single-stranded DNA or RNA with unique three-dimensional conformations, exhibit the ability to identify various targets, ranging from small molecules to tumor cells. Aptamers, also known as chemical antibodies, are generated by systematic evolution of ligands by exponential enrichment (SELEX) process and can function similarly to traditional antibodies. They hold numerous advantages over antibodies, such as ease of modification, low immunogenicity, and rapid tissue penetration and cell internalization due to their nucleic acid molecule structure. Since their discovery in the 1990s, aptamers have been widely used in biochemical analysis, disease detection, new drug research and other fields. This article provides an overview of aptamer selection and characterization for bladder cancer, discussing the research advancements involving aptamers in diagnosing and treating this disease. It covers aptamers obtained through different SELEX methods, including protein-SELEX, cell-SELEX, tissue-SELEX, and aptamers from other cancer SELEX; the detection in blood samples and urine samples; and application in targeted therapy and immunotherapy for bladder cancer. Currently, several aptamers capable of identifying bladder cancer have been generated, serving as molecular probes that have played a pivotal role in the early detection and treatment of bladder cancer. Bladder cancer perfusion therapy is well-suited for aptamer drug therapy because it does not require internal circulation, making it a suitable clinical indication for aptamer drug development. In addition, bladder cancer can be detected and monitored by collecting urine samples from patients, making it a preferred disease for clinical conversion of aptamers. While aptamers show promise, there is still much room for development compared with antibodies. There are still many clinically applied cancer biomarkers without corresponding aptamers, and more aptamers targeting different biomarkers should be selected and optimized to improve the sensitivity and accuracy for cancer detection and therapy. The field of aptamers urgently needs successful commercial products to promote its development, and home rapid detection/monitoring, imaging and targeted therapy of bladder cancer by infusion may be the breakthrough point for future application of aptamers.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.

Objective To study the distribution and function of growth hormone receptor(GHR)positive neurons in neonatal mouse brain.Methods Six GHR-CreERT;mTOMATO/mGFP fluorescent reporter gene mice were selected.All of them were induced with tamoxifen on the 3rd day after birth.On the 10th and 17th day,3 mice were sampled respectively at each time point.The distribution of GHR-positive neurons in the developing brain was observed at different stages.GHR floxed mice were generated.By crossing them with neuron-specific Thy1-CreERT;YFP mice,GHR in neurons was inducingly knocked out.Control mice(GHR fl/fl,4 mice)and conditional knockout mice(Thy1-CreERT;YFP;GHR fl/fl,4 mice)were induced on the 3rd day after birth.Samples were collected on the 10th day for observing the effect of neuronal GHR signaling on brain development.Results The GHR fluorescent reporter gene mice showed that GHR-positive cells were widely expressed in the developing mouse brain.GHR-positive neurons were concentrated in the paraventricular hypothalamic nucleus(PVN).After specifically knocking out GHR in neurons of the developing mouse brain,no significant differences were observed in the areal densities of neurons and various types of glial cells.Conclusion GHR-positive neurons are mainly concentrated in the PVN.Knocking out GHR in neurons of the developing mouse brain can not significantly change the morphology and density of various neural cell types.

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.

AIM:To investigate the mechanism of curcumin inhibiting the choroidal neovascularization(CNV)of brown Norway(BN)rats.METHODS: CNV model of 36 BN rats was established through laser photocoagulation induction, and they were divided into 6 groups with 6 rats in each group. Normal group was fed normally with no intervention, while 532nm laser photocoagulation was used to establish a experimental CNV model in BN rats. Rats after modeling were respectively intervened for 14d and divided into model group, ranibizumab group, curcumin low [100mg/(kg·d)], medium [200mg/(kg·d)], and high [400mg/(kg·d)] dose group. The model group was given intragastric administration of saline for 14d, ranibizumab(10mg/mL, 0.2mL/dose)was injected at 2d after photocoagulation with 5μL once for rats in ranibizumab group, and different concentrations of curcumin were intragastrically administrated to the rats in low, medium and high groups for 14d. Fundus photography, fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA)examination were performed at 14d after photocoagulation. Ocular histopathological specimens of rats with CNV were made, and the central thickness of CNV were observed by HE staining. Ocular histopathological specimens were made, and the expressions of AKT/p-AKT/HIF-1α/VEGF signaling pathway-related proteins were observed by immunohistochemistry. The mRNA relative expressions of AKT/HIF-1α/VEGF factor in CNV tissues were detected by RT-qPCR, and the protein expressions of AKT/p-AKT/HIF-1α/VEGF factor in CNV tissues were detected by Western-blot.RESULTS: CNV generation rates in the model group, the ranibizumab group, and the low, medium and high-dose curcumin groups were 78.18%, 73.21%, 77.19%, 75.86%, 74.55%, respectively, which were higher than 70%. The average absorbance were 182.12±6.59, 119.22±8.03, 166.45±8.33, 164.34±5.69, 149.22±6.45, respectively; the ranibizumab group was significantly lower than the model group(P<0.05); the low-dose, medium-dose and high-dose groups were significantly higher than the ranibizumab group(P<0.05), and the curcumin high-dose group was significantly lower than the model group(P<0.05). HE staining showed that the retinal tissue structure of BN rats in normal group was clear and neatly arranged. The central thickness of CNV in the ranibizumab group was significantly reduced at 14d after photocoagulation compared with the model group(P<0.05); While the curcumin high-dose group was significantly reduced compared with the model group(P<0.05), but increased when compared with ranibizumab group(P<0.05). Immunohistochemistry results showed that AKT, p-AKT, HIF-1α, and VEGF factors were negatively expressed in the retinal tissue structure of BN rats in the normal group, and no brown-yellow reactants were found. The expression of AKT, p-AKT, HIF-1α, and VEGF factors in the model group were higher than that in the normal group at 14d after photocoagulation(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While the expression of the curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). The mRNA results showed that the relative expression levels of AKT, HIF-1α and VEGF mRNA in the model group at 14d after photocoagulation were higher than those of the normal group(P<0.05); the ranibizumab group was lower than the model group(P<0.05). While curcumin high-dose group was significantly decreased compared with the model group(P<0.05), but significantly increased when compared with ranibizumab group(P<0.05). Western-blot results showed that there was no significant difference in the relative expression of AKT protein among each experimental groups at 14d after photocoagulation. The relative expression of p-AKT protein in the model group was significantly higher than that in the normal group(P<0.05); the ranibizumab group was significantly lower than the model group(P<0.05); the curcumin high-dose group was significantly lower than the model group(P<0.05). The relative expression levels of HIF-1α protein were significantly higher in the model group than in the normal group(P<0.05), and the ranibizumab group was lower than in the model group(P<0.05). The relative expression levels of HIF-1α protein was lower in the curcumin high-dose group than in the model group(P<0.05)but higher than ranibizumab group(P<0.05). The relative expression level of VEGF protein was significantly lower in the curcumin medium/high-dose group than in the model group(P<0.05).CONCLUSION: Curcumin at 400mg/(kg·d)has an inhibitory effect on CNV in BN rats. The mechanism may be closely related to inhibiting the activation of AKT/p-AKT/HIF-1α/VEGF signaling pathways.

Five compounds were isolated from the ethyl acetate fraction of Semen Persicae by using various chromatographic methods, including ODS, Sephadex LH-20, HPLC and semipreparative HPLC. Their structures were identified by 1D-NMR, 2D-NMR, HR-ESI-MS, UV, IR, circular dichroism (CD) and ECD calculation techniques: (2R,3R)-5,7,4′-trihydroxy-3′-methoxy-3-formylflavan-3-ol-5-O-β-D-glucopyranoside (1), (7R,8S)-dihydrodehydrodiconiferyl 6″-benzoyl alcohol-9-O-β-D-glucopyranoside (2), (7R,8S)-dihydrodehydrodiconiferyl alcohol-9-β-O-D-glucopyranosid (3), 2-methoxy-4-(2-propenyl)-phenyl-O-β-D-glucopyranoside (4), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol (5). Compound 1 and 2 are new compounds, and compounds 3-5 were obtained from Prunus davidiana (Carr.) Franch. for the first time.

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; Neoplasm Staging ; Lymphatic Metastasis ; Lymph Node Excision ; Retrospective Studies ; Prognosis ; Chemoradiotherapy/methods* ; Carcinoma, Squamous Cell/pathology*