ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Objective To study the effects of different SBRT-VMAT plans for non-small cell lung cancer(NSCLC)with unilateral ipsilateral double metastatic lesions on received dose,monitor unit(MU),conformity index(CI)and gradient index(GI)of the lung,so as to provide references for therapy planning of the patient above.Methods A total of 11 NSCLC patients with unilateral ipsilateral double metastatic lesions were selected,with three plans developed for each patient by the volumetric modulated arc therapy(VMAT).The inner target areas ITV1 and ITV2 were contoured based on the maximum projection image of the 4D-CT localization mode,which were uniformly expanded externally by 3 mm to obtain the plan target area PTV1 and PTV2,and then PTV1 was added with PTV2 to get PTV12.The first planning mode had the centers of PTV1 and PTV2 target areas as the treatment centers,and two separate plans of plan-1 and plan-2 were developed and then combined into a plan-sum plan for dose evaluation;the second planning mode had the centers of PTV1 and PTV2 target areas as the treatment center,resepctively,and a multicenter plan(plan-D)was formed.The third planning mode had the center of PTV12 target area as the treatment center,and a single-center plan(plan-S)was designed.To meet the requirements of prescribed dose,plan-1 and plan-2 of plan-sum were normalized to PTV1 and PTV2 95％volume and plan-S and plan-D were normalized to PTV 12 95％volume.The three planning modes were compared in terms of received dose,MU,CI and GI of the lung.SPSS 25.0 software was carried out for statistical analysis.Results Plan-S had no significant differences with Plan-sum except V5(P＞0.05),whose V10,V20,V30 and mean dose were significantly lower than those of plan-sum(P＜0.05);plan-D had its received dose and mean dose statistically lower than those of plan-sum(P＜0.05);plan-S and plan-D had no obvious differences in received dose of the lung(P＞0.05).Plan-sum had the CI significantly lower than those of plan-S and plan-D(P＜0.05);plan-S and plan-D had no statistically differences in CI(P＞0.05).Plan-D had the GI significantly lower than plan-S and plan-sum(P＜0.05).Plan-S and plan-sum had no significant differences in GI(P＞0.05).Plan-D and plan-sum had no statistical differences in MU(P＞0.05),which had the MUs significantly higher than that of plan-S(P＜0.05).Conclusion A multicenter planning mode may be used for optimizing dose distribution and enhancing conformity in case the patient can tolerate prolonged immobilization in a fixed position,and a singlecenter planning mode should be adopted to shorten treatment time when the patient is in poor physical conditions.[Chinese Medical Equipment Journal,2024,45(10):49-53]

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Chemokine signal pathways are important for the regulation of tumour metastasis. Chemokine receptors CXCR4 (C-X-C chemokine receptor type 4) and XCR1 (chemokine XC receptor 1) are involved in the metastasis of breast cancer, while the interaction between them remains unclear. Here we first identified the interaction between CXCR4 and XCR1 based on membrane protein yeast two-hybrid assays. Bioluminescence resonance energy transfer (BRET) showed that XCR1 could competitively bind to CXCR4 to form a heterodimer (P < 0.01). Results of wound healing assays via transient transfection of XCR1 and CXCR4 into HEK293 cells showed that 41.55% of the migration area rate in the co-transformation group was lower than 58.75% in the CXCR4-alone group after adding 30 nmol/L S D F-β. The co-expression of XCR1 inhibited the cellular motility, possibly mediated by the SDF-1β (stromal cell-derived factor 1)/CXCR4 signal pathway (P < 0.05). Furthermore, CXCR4 on the cell surface after co-expression of XCR1 in CXCR4-EGFP transgenic HEK293 cells was detected by flow cytometry. And the result suggested that XCR1 could accelerate the internalization of CXCR4 into the heterodimer induced by 30 nmol/L SDF-1β (P<0.05), which increased the internalization rate from 14.38% to 64.10%. Finally, the phosphorylation of Akt and ERK, which were involved in cell proliferation and migration, respectively, were examined. After 10 minutes of SDF-1β stimulation, ERK phosphorylation in the CXCR4-alone group showed a 3.59-fold increase, whereas the increase of ERK phosphorylation in the co-transfected group was only 2.08-fold. Interestingly, heterodimer formation reduced the phosphorylation level of ERK and shortened the activation time, whereas the phosphorylation level of Akt remained unchanged. Collectively, our findings revealed the hetero-dimerization of CXCR4 and XCR1 and its effects on CXCR4-mediated cellular motility, receptor internalization, and ERK pathway phosphorylation. Therefore, XCR1-targeting drugs could be candidates for cross-desensitization of CXCR4 and might represent a possible option for inhibiting breast cancer metastasis.

OBJECTIVE: To investigate the prognostic value of interim ¹⁸F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.
Fluorodeoxyglucose F18/therapeutic use* ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Thiamine

Objective:To investigate the effects of Buyang Huanwutang on the expression of microtubule-associated protein-2（MAP-2）， neurofilament-M（NF-M）， and growth associated protein-43（GAP-43）in rat sciatic nerve after sciatic nerve transection and anastomosis. To explore the mechanism of Buyang Huanwutang promoting peripheral nerve regeneration. Method:SD rats were selected as the experimental subjects， and sciatic nerve transection model was selected as the experimental model. They were randomly divided into model group， sham operation group， Buyang Huanwutang group high， medium and low dose （29.6， 14.8， 7.4 g·kg^-1）group， and mecobalamin （0.156 mg·kg^-1）group， the model group and the sham operation group were given distilled water intragastric administration. After successful modeling， each group was treated with relevant drugs for 4 weeks. After 4 weeks， sciatic nerve function index（SFI）， degree of inclined plate test and hematoxylin-eosin（HE）of sciatic nerve in each group were tested. The expression levels of MAP-2， NF-M， and GAP-43 at the sciatic nerve anastomosis site were detected by immunohistochemistry and Western blot. Result:Compared with sham operation group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in model group were significantly increased （P<0.01）. Compared with model group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in Buyang Huanwutang high， medium and low-dose groups were significantly increased （P<0.05，P<0.01）. Conclusion:Buyang Huanwutang has a positive effect on nerve regeneration after sciatic nerve transection and anastomosis in rats.

Objective: To define the current status and analyze the medical quality of interventional therapy for patients with atrial fibrillation (AF) in China. Methods: This survey was performed in all seven large regions of China, one to three regional major medical centers were selected from each region. Medical records of patients underwent interventional therapy for AF in the year 2017 were randomly inspected. CHA₂DS₂-VASc score, prescribed anticoagulant after ablation, indication of left atrial appendage occlusion (LAAO), and complications in the medical records were analyzed. Results: A total of 10 800 AF catheter ablations and 447 LAAOs were performed in 17 regional medical centers in 2017. There were 10/17 centers performing AF catheter ablation<500 cases and 7/17 centers performing LAAO<20 cases. A total of 1 347 cases of catheter ablation and 160 cases of LAAO were selected for further analysis. Among all selected cases, 15.8% (238/1 505) non-valvar AF cases recorded CHA₂DS₂-VASc scores. The anticoagulation rate after AF catheter ablation was 98.6% (1 328/1 347), anticoagulation rate was higher than 90% in 16 out of 17 centers. The complication and severe complication rates of AF catheter ablation were 0.9% (12/1 347) and 0.4% (5/1 347), respectively. The differences of complication and severe complication rates in AF catheter ablation were similar between centers performing<500 cases and centers performing ≥500 cases (0.5% (2/413) vs. 1.1% (10/934), P>0.05; 0.5% (2/413) vs. 0.3% (3/934), P>0.05). The coincidence rate of LAAO indication was 81.3% (130/160), and the rate was higher in center performing ≥20 cases than in centers performing<20 cases (84.8% (106/125) vs. 68.6% (24/35), P<0.05). The complication and severe complication rates of LAAO were 3.1% (5/160) and 1.9% (3/160). The rate of complications in LAAO was higher in center performing<20 cases than in centers performing ≥20 cases (8.6% (3/35) vs. 1.6% (2/125), P<0.05), and there was no significant difference in severe complication rate (5.7% (2/35) vs. 0.8% (1/125), P>0.05). Conclusions: Interventional therapy for AF in China is generally standardized and safe. The overall incidence of complications post AF interventional ablation is low, the anticoagulation rate after AF catheter ablation is high, and the adherence rate of LAAO indication is fair. The indicators mentioned above vary widely among centers.

OBJECTIVE: To identify the chaperone of polypyrimidine tractor-binding protein-associated splicing factor (PSF) in myeloid leukemia cells, and to explore the mechanism and redistributive pattern to cell surface of PSF in chemo-sensitive HL60 cells and resistant HL60/DOX cells. METHODS: The eukaryotic expression vector of PSF was transfected with liposomes transiently, then flow cytometry was used to detect the expression level of PSF on the cell surface 24 h, 48 h and 72 h after vector transfections. We constructed a chimeric expression vector, streptavidin binding peptide (SBP)-PSF, meanwhile this vector was transfected and made SBP-PSF fusion protein overexpress. In addition, we used streptavidin magnetic beads to precipitate the cellular chaperonin of PSF and then identified its chaperonin by mass spectrometry (MS). Lentiviral vectors containing cytokeratin18 (K18) interference sequences were transfected into 293T cells to prepare lentivirus. HL60 and HL60/DOX cells were infected with lentivirus to obtain stable interfering K18 cell lines. Next, flow cytometry was used to test the membrane relocation level of PSF. Together, these methods confirmed the similar or different mechanisms of the PSF redistributing to membrane synergistically mediated by K18 in HL60 and HL60/DOX cells. RESULTS: The expression of membrane relocated PSF was detected every day for three days (at the end of 24 h, 48 h and 72 h) after transient overexpression. The expressing rate of PSF on the cell surface was 22.4%±3.5%, 37.9%±6.0%, 58.3%±8.8%, respectively in sensitive HL60 cells, while that was 4.7%±0.5%, 3.9%±0.6%, 2.9%±0.6% , respectively in resistant HL60/DOX cells. The difference of expressing rate on each day was significant, P<0.01. We identified K18 detected by co-immunoprecipitation and mass spectrum assay which was the cellular chaperone of PSF. We found that K18 knockdown decreased the PSF expression level which redistributed on cell surface from 48.9%±5.4% to 6.2%±1.0% in sensitive HL60 cells, and from 9.11%±1.2% to 2.21%±0.51% in resistant HL60/DOX cells, respectively. CONCLUSION K18 is the intracellular chaperonin of PSF. The interaction of PSF and K18 mediates its redistribution to cell membrane in sensitive cells. While in resistant cells, PSF failed to relocate at the cell surface and accumulated in cells, which mediated resistance to chemotherapeutics.
Cell Membrane ; Doxorubicin ; Drug Resistance, Multiple ; Humans ; Keratin-18/metabolism* ; Leukemia, Myeloid

OBJECTIVE: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML). METHODS: The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis. RESULTS: Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed. CONCLUSION UCBT is an effective treatment for children with JMML.
Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myelomonocytic, Juvenile ; Male ; Retrospective Studies ; Transplantation Conditioning