The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NP_FeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H₂S amplification. The bioactive NP_FeS/GD exhibited controlled release of GSDMD plasmid, H₂S, and Fe²⁺ in response to the tumor microenvironment. Fe²⁺, H₂S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H₂S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NP_FeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H₂S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.

This study aims to construct C57/B6-L and A549 cell lines that stably overexpress circu-lar RNA LAMP3(circLAMP3),laying the foundation for further research on the biological func-tions of circLAMP3.Total RNA was extracted and reverse transcripted into cDNA from C57/B6-L and A549 cells to amplify the full-length sequence of circLAMP3.Then,the fragments of cir-cLAMP3 were ligated into pLC5-ciR vector to obtain pLC5-Mouse-circLAMP3 and pLC5-Human-circLAMP3 recombinant plasmids.The lentiviruses expressing circLAMP3 were packaged on tran-sient transfected HEK293T cells.C57/B6-L and A549 cells were infected with lentiviruses to gen-erate cell lines overexpressing circLAMP3 through puromycin screening.To verify the overexpres-sion efficiency of circLAMP3 of cell lines,we performed the fluorescence microscopy,PCR amplifi-cation,quantitative PCR(qPCR),and Sanger sequencing experiments.The results indicated that the overexpression plasmids of pLC5-Mouse-circLAMP3 and pLC5-Human-circLAMP3 were suc-cessfully constructed.Strong green fluorescence was observed under a fluorescence microscopy.C57/B6-L and A549 cell lines showed a significant increase in the expression of circLAMP3 by PCR and qPCR methods.Sanger sequencing results showed that the junction site of circLAMP3 was correct.This study successfully constructed C57/B6-L and A549 cell lines overexpressing circLAMP3,providing biomaterials for further exploration of the biological function of circLAMP3 in influenza virus replication.

Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ² = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.

In recent years, mRNA drugs have shown a great potential for the treatment of genetic diseases and attracted the attention of many researchers. This article has reviewed the advance in the research of mRNA drugs for the treatment of genetic diseases over the past 30 years, including their mechanisms of action and structure design, with a focus on their advantages as alternative therapies such as high specificity, low dosage, and sustained expression. Meanwhile, challenges for the effective delivery and storage methods for the mRNA drugs are discussed, with an aim to provide guidance for subsequent researches.

Objective To explore the feasibility of quartz glass for radiotherapy dosimetry through the experimental study of the thermoluminescence characteristics of synthetic quartz glass. Methods The thermoluminescence glow curves of quartz glass under different annealing conditions were analyzed, the thermoluminescence characteristics of quartz glass were studied, and the measurement parameters were optimized. Using the Co-60 reference radiation field in the National Secondary Standard Dosimetry Laboratory, the quartz glass samples under different annealing conditions were irradiated following the dose levels of radiotherapy, i.e., 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 Gy, respectively. According to the relationship between the absorbed dose of quartz glass and the relative thermoluminescence signal intensity, the linearity and dispersion of the dose response of quartz glass were obtained, and the feasibility of quartz glass for radiotherapy dosimetry was analyzed. Results The linear correlation coefficient of dose response of quartz glass under annealing condition of 430℃ for 10 min was 0.9984, and the dose response dispersion was 0.97% at the absorbed dose of 2 Gy. The linear correlation coefficient of dose response of quartz glass under annealing condition of 600℃ for 1 h was 0.9911, and the dose response dispersion was 1.4% at the absorbed dose of 2 Gy. Conclusion Preliminary results suggest that quartz glass with annealing condition of 430℃ for 10 min has the potential to be used for radiotherapy dosimetry.

Objective:To investigate whether the cyclosporin A (CsA) can improve the blastocyst implantation with mild impaired of trophoblast cells of mice.Methods:1) Totally 30 ICR mice were intraperitoneally injected with 5 mg/kg CsA, then the blood concentrations of CsA in mice were detected at 1 h, 3 h, 4 h, 6 h, 8 h, 10 h, 13 h, 14 h, 16 h and 20 h after administration using chemiluminescence method. 2) A total of 36 mice were randomly divided into control group and experimental group (CsA group); the experimental group was intraperitoneally injected with 5 mg/kg CsA and control group was injected with the equivalent dose olive oil of the same body weight. Embryos were classified into A, B, C types according to the guidelines of Gardner and experimental needs. Embryos were transferred to the uterus in the two groups. The embryo implantation rate was calculated and the leukemia inhibitory factor (LIF) mRNA level was measured by real time fluorescence quantitative PCR in 5.5 d postcoitum (dpc).Results:1) The blood concentration of CsA in mice reached a peak at 6-10 h after administration. 2) The embryo implantation rate of B type [73.9% (34/46)] had significantly improved in experimental group [50.0% (23/46), P=0.018]. 3) The expression of LIF mRNA level was not significantly different between the two groups ( P>0.05). Conclusion:When CsA was administered at a dose of 5 mg/kg, CsA can improve the embryo implantation rate with mild impaired trophoblast cells. CsA might become a potential drug to increase the success rates of the in vitro fertilization.

Objective:To investigate whether the cyclosporin A (CsA) can improve the blastocyst implantation with mild impaired of trophoblast cells of mice.Methods:1) Totally 30 ICR mice were intraperitoneally injected with 5 mg/kg CsA, then the blood concentrations of CsA in mice were detected at 1 h, 3 h, 4 h, 6 h, 8 h, 10 h, 13 h, 14 h, 16 h and 20 h after administration using chemiluminescence method. 2) A total of 36 mice were randomly divided into control group and experimental group (CsA group); the experimental group was intraperitoneally injected with 5 mg/kg CsA and control group was injected with the equivalent dose olive oil of the same body weight. Embryos were classified into A, B, C types according to the guidelines of Gardner and experimental needs. Embryos were transferred to the uterus in the two groups. The embryo implantation rate was calculated and the leukemia inhibitory factor (LIF) mRNA level was measured by real time fluorescence quantitative PCR in 5.5 d postcoitum (dpc).Results:1) The blood concentration of CsA in mice reached a peak at 6-10 h after administration. 2) The embryo implantation rate of B type [73.9% (34/46)] had significantly improved in experimental group [50.0% (23/46), P=0.018]. 3) The expression of LIF mRNA level was not significantly different between the two groups ( P>0.05). Conclusion:When CsA was administered at a dose of 5 mg/kg, CsA can improve the embryo implantation rate with mild impaired trophoblast cells. CsA might become a potential drug to increase the success rates of the in vitro fertilization.

Long noncoding RNAs (lncRNAs) are a class of RNA molecules that are greater than 200 nt in length and do not have protein-coding capabilities or encode micropeptides only. LncRNAs are involved in the regulation of cell proliferation, differentiation, apoptosis and other biological processes, and are closely associated with the occurrence, recurrence and metastasis of a variety of malignant hematologic diseases. This article summarizes the function, regulatory mechanism and potential clinical application of lncRNAs in leukemia. In general, lncRNAs regulate the occurrence and development of leukemia and the multi-drug resistance in chemotherapy through epigenetic modification, ribosomal RNA transcription, competitive binding with miRNA, modulating glucose metabolic pathway, and activating tumor-related signaling pathway. Studies on lncRNAs provide new references for understanding the pathogenesis of leukemia, uncovering new prognostic markers and potential therapeutic targets, and addressing the problems of drug resistance and post-treatment recurrence in patients in clinical treatment of leukemia.
Cell Proliferation ; Humans ; Leukemia/genetics* ; MicroRNAs ; Neoplasms ; RNA, Long Noncoding/genetics*

Human acute leukemia (AL) is a clonal malignancy with abnormal hematopoietic stem cells. Clinically, AL is very difficult to cure due to its sudden onset and short course of disease progression. Previous studies have shown that eukaryotic initiation factor 4B (eIF4B) plays a critical role in the development of chronic leukemia. However, the involvement of eIF4B in human acute leukemia is still largely unknown. Therefore, we studied eIF4B function and its regulatory mechanism in human acute leukemia. We found that phosphorylation levels of eIF4B in acute leukemia cells were significantly reduced in response to treatment with either LY294002 (PI3K inhibitor), AKTi (AKT inhibitor) or SMI-4A (Pim inhibitor). Co-treatment with inhibitors targeting JAK/STAT5/Pim and PI3K/AKT/mTOR signaling dramatically promoted apoptosis of acute leukemia cells by downregulating eIF4B phosphorylation. Furthermore, in vitro and in vivo functional experiments showed that eIF4B played an important anti-apoptosis role in the acute leukemia cells by regulating the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL. In contrast, silencing eIF4B inhibited the growth of acute leukemia cells as engrafted tumors in nude mice. Taken together, our results indicate the synergistic role of JAK/STAT5/Pim and PI3K/AKT/mTOR signaling pathways in regulating eIF4B phosphorylation in acute leukemia, and highlight eIF4B as a candidate therapeutic target for treatment of acute leukemia.
Animals ; Apoptosis ; Cell Line, Tumor ; Leukemia ; Mice ; Mice, Nude ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; STAT5 Transcription Factor/metabolism*

Objective To evaluate the curative effect of robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for early stage lung cancer patients. Methods We retrospectively analyzed the clinical data of 80 patients with radical resection of lung cancer in Gansu Provincial Hospital between January 2016 and December 2017. The patients were divided into two groups: 43 patients in a VATS group and 37 in a RATS group. There were 51 males and 29 females. Data were processed with STATA v14.0 statistical software. Results There were significant differences in the operative time, duration of hospital stay and operative costs between the two groups. In the RATS group, operative duration was longer (172.21 minutes versus 162.20 minutes, P=0.018), cost was higher (74 076.69 yuan versus 54 814.73 yuan, P<0.001), and required significantly shorter hospital stay (8.27 daysversus 10.76 days, P=0.001) compared with those of the VATS group. There was no statistical difference between the two groups in terms of conversion (3 versus 0, P=0.144), blood loss during operation (61.29 ml versus 90.63 ml, P=0.213), dissected lymph node number (17.38 versus 12.63, P=0.095), drainage volume (1 406.76 ml versus 1 514.60 ml, P=0.617) and the drainage time (7.92 days versus 7.20 days, P=0.440). Conclusion In the early lung cancer patients who underwent thoracic surgery, the postoperative hospitalization time of the RATS group is shorter than that of the VATS group, and the operation time is longer than that of the VATS group. The other short-term surgical indexes are similar to those of thoracoscopic surgery. However, the robot has great advantages in the treatment of patients with difficult lymph node dissection, serious pleural adhesion and complicated anatomical relationship.