OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

Objective:To investigate the therapeutic efficacy and safety of conditioning regimen with oral melphalan in tandem autologous hematopoieticstem cell transplantation (ASCT) for patients with malignant plasma cell diseases.Methods:A retrospective case series study was conducted. The clinical data of 13 patients with malignant plasma cell diseases who underwent tandem ASCT between October 2019 and March 2024 in the First Affiliated Hospital of Xi'an Jiaotong University were collected. Compared with the use of intravenous melphalan as conditioning regimen for the first ASCT, hematopoietic reconstruction after transplantation, the therapeutic effects, adverse reactions after drug usage and survival of conditioning regimen with oral melphalan after tandem ASCT were analyzed.Results:Among the 13 patients, there were 10 males and 3 females, with a median age [ M ( Q1, Q3)] of 53 (48, 61) years; 11 cases were multiple myeloma and 2 cases were plasma cell leukemia. Before the first ASCT, tandem ASCT was performed 2-6 months later. The median reconstruction time of neutrophils after the first and second ASCT were both 9 (9, 10) d, and the median reconstruction time of platelets after the first and second ASCT were both 10 (9, 11) d, and there were no statistically significant differences in reconstruction rate of granulocytes on day 9 [69.2% (9/13) vs. 61.5% (8/13)] and platelets on day 10 [46.2% (6/13) vs. 53.8% (7/13)] between the first and second transplantation (all P > 0.05). There were 4 cases of strict complete remission (sCR), 3 cases of complete remission (CR), 4 cases of very good partial remission (VGPR), and 2 cases of partial remission (PR) before the first ASCT. After the first ASCT 1 month later, 1 case achieved VGPR, 1 case achieved PR, 11 cases achieved sCR; all 13 patients achieved sCR at 6 months after second ASCT. Compared with conditioning regimen of intravenous melphalan for the first ASCT, the non-hematological adverse reactions such as nausea (7 cases vs. 9 cases), vomiting (4 cases vs. 13 cases), diarrhea (4 cases vs. 13 cases) and oral mucositis (2 cases vs. 9 cases) in the conditioning regimen of oral melphalan after the second ASCT was reduced, and the differences were statistically significant (all P < 0.01). After the 2 transplantation conditioning regimen with melphalan, Ⅳ degree myelosuppression occurred in 13 cases. After the second ASCT, the median follow-up time was 14 (10, 22) months, 7 patients received maintenance therapy containing lenalidomide, 3 patients received maintenance therapy containing bortezomib, 2 patients received pomalidomide maintenance therapy, and 1 patient received maintenance therapy containing CD38 monoclonal antibody. At the last follow-up, all patients survived, among which 6 multiple myeloma patients relapsed; and the median recurrence time was 13 (10, 22) months after the second ASCT. The estimated 5-year progression-free survival rate was 28.6%. Conclusions:Conditioning regimen with oral melphalan for the second ASCT is safe and well tolerated, and it may further improve the efficacy of the first transplantation.

Objective To study the clinical efficacy of Xiaoqinglong decoction combined with the conventional protocol of western medicine in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)presenting with exterior cold and interior fluid retention syndrome,and to evaluate its effect on the short-term prognosis of patients.Methods A total of 124 AECOPD patients presenting exterior cold and interior fluid retention syndrome were divided into an observation group(62 cases)and a control group(62 cases)using a random number table.Patients in the control and observation groups were managed with conventional western medicine treatment protocols consisting of bronchodilators,glucocorticoids,and antibacterial drugs.In addition,patients in the observation group were also given Xiaoqinglong decoction at one dose per day for 10 days in succession.The primary outcome indicators included the total effective treatment rate and the main traditional Chinese medicine(TCM)syndrome scores before treatment and after 10 days of Xiaoqinglong decoction treatment.The secondary outcome indicators included infection and inflammatory indicators,including white blood cell count(WBC),procalcitonin(PCT),interleukin(IL)-6,C-reactive protein(CRP),and arterial blood gas indicators,including arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),and arterial oxygen saturation(SaO2),measured before treatment and after 10 days of treatment,adverse drug reactions during treatment,and the severity of dyspnea assessed by the modified Medical Research Council(mMRC)dyspnea scale at the 1-month follow-up after discharge.Results Compared with baseline findings for the same group before treatment,the main TCM syndrome scores and the total score were reduced in both groups after treatment(P<0.05).After treatment,compared with those of the control group,the syndrome scores for cough,aversion to cold,nasal congestion,and runny nose,and the total score in the observation group were lower(P<0.05).The total effective treatment rate in the observation group(94.91%)was significantly higher than that in the control group(82.76%)(P<0.05).After 10 days of treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in both groups were significantly reduced compared with those before treatment(P<0.05).After treatment,the levels of PaCO2,WBC,PCT,IL-6,and CRP in the observation group were lower than those in the control group(P<0.05).Compared with those before treatment,PaO2 and SaO2 levels in both groups increased significantly after 10 days of treatment(P<0.05).During the course of treatment,no severe adverse reactions,such as liver or kidney dysfunction,occurred in either group.No adverse reactions associated with Xiaoqinglong decoction were observed.No patients in either group reached mMRC grade 4 at the 1-month follow-up after discharge.The mMRC grades in both groups declined at the 1-month follow-up after discharge compared to those before treatment(P<0.05).At the 1-month follow-up after discharge,the mMRC grades of patients in the observation group were lower than those of the control group(P<0.05).Conclusion Xiaoqinglong decoction combined with the conventional protocol of western medicine deminstrates good clinical efficacy in treating patients with AECOPD of exterior cold and interior fluid retention syndrome,and can effectively improve the TCM syndromes,relieve the symptoms of dyspnea,reduce the inflammatory response,promote the resolution of infection,delay disease progression,improve short-term prognosis,and shows better safety.

More than 70%of tumor patients require radiotherapy.Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy.With the application of artificial intelligence technology in medical electron linear accelerator,radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy.This study introduces the development history,working principles and system composition of medical electron linear accelerators.It outlines the key technologies for improving the performance of medical linear electron accelerators,including beam control,multi-leaf collimator,guiding technology and dose evaluation.It also looks forward to the development trend of major radiotherapy technologies,such as biological guided radiotherapy,FLASH radiotherapy and intelligent radiotherapy,which provides references for the development of medical electron linear accelerators.

Objective To analyze the feasibility and efficacy of a deep convolutional neural network(DCNN)model based on chest CT images to evaluate bone mineral density(BMD).Methods A total of 1 048 health check subjects'2 096 central level images of lumbar 1 and 2 vertebral bodies were used for experiments and analysis in this retrospective study.According to the results of quanti-tative computed tomography(QCT)BMD measurement,the subjects were divided into three categories:normal,osteopenia,osteopo-rosis(OP).Herein,a DCNN segmentation model was constructed based on chest CT images[training set(n=1 096),tuning set(n=200),and test set(n=800)],the segmentation performance was evaluated using the Dice similarity coefficient(DSC)to com-pare the consistency with the manually sketched region of vertebral body.Then,the DCNN classification models 1(fusion feature construction of lumbar 1 and 2 vertebral bodies)and model 2(image feature construction of lumbar 1 alone)was developed based on the training set(n=530).Model performance was compared in a test set(n=418)by the receiver operating characteristic(ROC)curve analysis.Results When the number of images in the training set(n=300)was adopted,the DSC value was 0.950 in the test set.The results showed that the sensitivity,specificity and area under the curve(AUC)of model 1 and model 2 in diagno-sing osteopenia and OP were 0.716,0.960,0.952;0.941,0.948,0.980;0.638,0.954,0.940;0.843,0.959,0.978,respectively.The AUC value of normal model 1 was higher than that of model 2(0.990 vs 0.983,P=0.033),while there was no significant difference in AUC values between osteopenia and OP(P=0.210,0.546).Conclusion A DCNN may have the potential to evaluate bone mass based on chest CT images,which is expected to become an effective tool for OP screening.

Lymphoma-associated hemophagocytic syndrome is aggressive with rapid progression, particularly in NK/T cell lymphoma. The MINE regimen is a salvage treatment for aggressive non-Hodgkin lymphoma. In our center, the modified MINE regimen was applied to treat three patients with hemophagocytic syndrome secondary to aggressive NK cell leukemia and T-cell lymphoma. The modified MINE regimen showed good efficacy against NK/T cell lymphoma, control of the inflammatory state of secondary hemophagocytic syndrome, and good tolerability.

BACKGROUND: There is a high morbidity, mortality, and poor clinical prognosis of lung squamous cell carcinoma (LUSC). However, there is currently no effective targeted treatment plan for LUSC. As a long non-coding RNA (lncRNA), lncRNA miR143HG has been proven to play an important role in the occurrence and development of various tumors. However, the biological role played by lncRNA miR143HG in LUSC cells is still unclear. Therefore, this study aimed to investigate the mechanism of lncRNA miR143HG on regulating the biological behavior of LUSC H520 cells. METHODS: Pan-cancer analysis and differential expression analysis of lncRNA miR143HG were performed based on The Cancer Genome Atlas (TCGA) database. The predictive effect of lncRNA miR143HG on the diagnosis and prognosis of LUSC was evaluated by adopting the receiver operating characteristic (ROC) curve and timeROC curve. The enrichment degree of each pathway to lncRNA miR143HG was determined. The expression of lncRNA miR143HG and miR-155 in BEAS-2B cells and H520 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). H520 cells were randomly divided into blank control group (without any treatment), negative control group (transfected with lncRNA-NC), lncRNA miR143HG group (transfected with lncRNA miR143HG), and lncRNA miR143HG+miR-155 group (co-transfected with lncRNA miR143HG and miR-155). The approaches of CCK-8, wound healing test, Transwell assay, flow cytometry, qRT-PCR, and Western blot were respectively employed to detect the cell proliferation ability, cell migration ability, cell invasion ability, cell apoptosis rate, and expression level of related genes and proteins of the Wnt/β-Catenin pathway. RESULTS: The results of pan-cancer analysis and differential analysis collectively showed that except for renal clear cell carcinoma, the expression of lncRNA miR143HG in other cancer tissues was higher than that in healthy tissues, and the differences were significant in LUSC. The evaluation results of the ROC curve and timeROC curve suggested that lncRNA miR143HG was of great significance in the prediction of diagnosis and prognosis of LUSC. The pathways enriched in high expression of lncRNA miR143HG mainly included focal adhesion, vascular smooth muscle contraction, calcium signaling pathways, and so on; the pathways enriched in the low expression of lncRNA miR143HG embraced oxidative phosphorylation, cell cycle, basic transcription factors, etc. The qRT-PCR results showed that lncRNA miR143HG was low expressed but miR-155 was highly expressed in H520 cells when compared to BEAS-2B cells (P<0.05). Compared with the negative control group, the expression levels of the gene of lncRNA miR143HG, the gene and protein of Wnt, as well as the gene and protein of β-Catenin were significantly increased, while the gene expression of miR-155, the ability of cell proliferation, cell migration, and cell invasion were significantly reduced, but the cell apoptosis rate was dominantly elevated in cells of lncRNA miR143HG group (P<0.05). In addition, compared with the lncRNA miR143HG group, overexpression of miR-155 could reverse the biological behavior mediated by lncRNA miR143HG, and the difference was statistically significant (P<0.05). CONCLUSIONS LncRNA miR143HG was of great significance for the biological behavior of H520 cells. LncRNA miR143HG inhibited the ability of proliferation, migration, and invasion, as well as enhanced the apoptosis of H520 cells by downregulating miR-155 expression, which may be related to the Wnt/β-Catenin pathway.
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Humans ; RNA, Long Noncoding/genetics* ; beta Catenin/metabolism* ; Lung Neoplasms/genetics* ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; MicroRNAs/genetics* ; Lung/pathology* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.