Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

Objective     To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods     Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion     For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.

Here we summarized novel Chimeric antigen receptor T-cell immunotherapy (CAR-T) based on the immune material aspect. Young healthy donor T cells, stem cell-like memory T cells, human induced pluripotent stem cells and umbilical cord blood T cells are all potential candidates to enhance CAR-T cell therapy depending on their anti-tumor efficacy. Besides, due to less restricted major histocompatibility complex (MHC) mismatch effect, viral specific T cells, γδT cells, invariant natural killer T cells and macrophages also become idealized T cell sources in terms of Universal CAR-T (UCAR-T) cell therapeutics. In addition, studies demonstrated that more balanced CD4 +/CD8 + T cell ratio and eliminating monocytes during leukapheresis have a positive influence on CAR-T cell functioning, whereas T cells with higher exhaustion markers expression hampers anti-tumor ability of CAR-T cells after infusion. To avoid application of such T cells or mitigate the impact using immune checkpoint inhibitors is of great importance.

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

The meridian theory is the pioneer of clinical diagnosis and treatment of diseases in Traditional Chinese Medicine (TCM). From Shang Han Lun to Pi Wei Lun, the meridian theory has contributed important theoretical organization materials and clinical practice experience to the establishment of the diagnosis system of external and internal injuries. The acupoints contained in its clinical acupuncture and moxibustion record symptoms, and some laws summarized have been absorbed and used for reference. It shows the positive significance of its exploration in clinical diagnosis and treatment. A system of differentiation and treatment of external and internal injuries with acupuncture has not been formed, even though the meridian theory of TCM has a long history with many areas being explored, such as diseases, acupoints, acupuncture methods and stimulation amount. Therefore, this paper starts from the academic development history of meridians, reviews and analyzes the contribution and limitations of TCM acupuncture and moxibustion in the diagnosis and treatment of internal injury, in order to enlighten the current study and understanding of TCM.

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.

Objective To observe the effect of excretory/secretory products from Trichinella spiralis adult worms(AES)on cecal ligation and puncture(CLP)?induced sepsis in mice. Methods Forty?eight BALB/c mice were randomly divided into 3 groups:a sham operation group(PBS+sham group,Group A),a CLP?induced sepsis group(PBS+CLP group,Group B)and an AES treatment group(AES+ CLP group,Group C). The mice of each group were intraperitoneally injected with 25 μg of AES or PBS only as a control in a total volume of 200μl. Eight mice from each group were selected randomly for survival analy?sis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung,liver and kidney tissues by HE staining 12 h after CLP,and then determined for the detection of cytokines including TNF?α,IL?1β,IL?6,IL?10 and TGF? βin the sera by ELISA. Results The difference among the survival rates of mice in the 3 groups was statistically significant (χ2=21.16,P<0.05). Compared to Group A(100%),the survival rate of mice in Group B(0)decreased significantly(P<0.05),and also the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group B increased signifi?cantly after CLP. Compared with the mice in group B,the survival rate of those in Group C(70%)increased significantly(P<0.05),and the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro?inflammatory cytokines TNF?α(F=27.11,P<0.05),IL?1β(F=18.75,P<0.05)and IL?6(F=100.93,P<0.05)in the sera of the mice in the three groups were statistically signifi?cant. Compared with the mice in Group A,the levels of the 3 cytokines of those in Group B increased significantly(all P <0.05). However,after the treatment with AES,the levels of the pro?inflammatory cytokines of those in Group C decreased signifi?cantly(all P<0.05). The differences among the levels of immunoregulatory cytokines IL?10(F=10.88,P<0.05)and TGF?β(F=11.37,P<0.05)in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B,the levels of IL?10 and TGF?β of those in Group C were higher after treatment with AES(both P<0.05). Conclu?sion T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.

Background and purpose:The morbidity and mortality of lung cancer are currently the highest malignant tumor in China and the world. Most onset age of the illness is after 60 years old. Therefore, surgical resection of lung cancer in the elderly is very worthy of concern. This study aimed to investigate the clinical features, epidemic characteristics and conditions in perioperative period between the elderly and middle-aged patients with lung cancer, and provide the reference for clinical treatment.Methods:Totally 1 019 patients with lung cancer who were admitted to the hospital and accepted the operations in department of thoracic surgery in Shanghai Pulmonary Hospital from Jan. 2007 to Dec. 2012 were analysed retrospectively. The clinical data including gender, pathological type, TNM stage, intraoperative amount of bleeding and post-operative length of hospitalization were compared.Results:There was a signiifcant difference in sexual factors between these two groups (P?0.05), and compared with the middle-aged group, the proportion of male was more higher in the elderly group (76.91%vs 52.81%). Adenocarcinoma was the most common and squamous carcinoma was the next in both two groups. The constituent ratio of the pathlogical type between the elderly group and the middle-aged group was statistically signiifcant (P?0.05). The squamous carcinoma in the elderly group was higher than that in the middle-aged group (37.5%vs 15.6%). On the contrary, adenocarcinoma was more common in the middle-aged group (72.8%vs 50.7%). StagesⅡa,Ⅱb, andⅢa were more common in the elderly group and stagesⅠa, andⅠb were the most clinical stage in the middle-aged group. The clinical stage between two groups was statistically significant (P?0.05).The intraoperative amount of bleeding was higher and the post-operative length of hospitalization was longer in the elderly group, with a signiifcant difference as compared with that in the middle-aged group(P?0.05). And there was a signiifcant difference in incidence of accompanying diseases between the two groups, compared with the middle-aged group, the proportion of accompanying diseases was more higher in the elderly group(58.6%vs42.3%).Conclusion:Elderly patients with lung cancer are more common in males, with adenocarcinoma being the most common. The cancer mostly belongs to a medium or advanced stage. Elderly patients have the trend with more amount of bleeding in operation and lengh of stay.

Objective To get a molluscicide from Reineckea carnea which is effective on Oncomelania hupensis but has low poison on fish. Methods Methyl soaking, column chromatography and HPLC were used for isolation of molluscicidal component from Reineckea carnea. Results The snail mortality with Reineckea carnea powder was 86.0% for 72 h immersion and 100.0% for 120 h at the concentration of 17.5 mg/L, but the fish mortality was 0 at the concentration of 130 mg/L, indicating that Reineckea carnea had different effects on the two kinds of animals . The fraction A was obtained from Reineckea carnea by methyl immersion, column chromatography. The snail mortality with A was 84.4% for 144 h at the concentration of 10 mg/L, indicating that A had high molluscicidal effect on Oncomelania hupensis. After A being isolated by HPLC, 99.98% RC-Ⅰ was obtained from it . RC-Ⅰ was determined by API2000 LC/MS and other spectrum, and it was deduced to be one of steroidal glycosides. Conclusion Reineckea carnea contains a high effective molluscicidal component.