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.

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.
Child ; Humans ; Cholesterol, HDL ; Cross-Sectional Studies ; Non-alcoholic Fatty Liver Disease/complications* ; Overweight/complications* ; Pediatric Obesity/epidemiology* ; Prevalence ; Adolescent

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Objective To explore the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on activity in the intact motor cortex controlling the suprahyoid muscles and thus on dysphagia after an unilateral stroke.Methods Forty patients suffering dysphagia more than two weeks after a unilateral cerebral stroke were randomly divided into an experimental group and a control group,each of 20.Both groups were given traditional swallowing rehabilitation training,while the experimental group was additionally provided with 5 Hz rTMS for two weeks.Before and after the treatment,all of the patients were characterized using X-ray fluoroscopy,video fluoroscopic swallowing study (VFSS) and surface electromyography,and their swallowing was evaluated using a standardized swallowing assessment (SSA) and a penetration-aspiration scale (PAS).Results After the treatment,significant improvement was observed in both groups in the average swallowing time and in the maximum amplitude of sEMG,as well as the average SSA,PAS and VFSS scores (P＜0.05).The average values in the experimental group were in all cases significantly better than the control group's averages (P＜0.05).Conclusion Applying rTMS at 5 Hz to the motor cortex of the contralateral hemisphere controlling the suprahyoid muscles can effectively improve unilateral-hemisphere dysphagia after stroke.

Objective　Dendritic cells (DCs), helper T cells 17 (Th17) and regulatory T cells (Treg) are closely related to the pathogenesis of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the changes of Th17- and Treg-related cytokines in the bronchoalveolar lavage fluid (BALF) of COPD mice after DC-based adoptive immunotherapy with over-expressed suppressor of cytokine signaling protein 1 (SOCS1) and provide some new ideas for the treatment of COPD.　Methods　A total of 48 male C57BL/6 mice were randomly divided into 5 groups: healthy control, COPD model control, immature DC (imDC), DC-SOCS1 1×106, and DC-SOCS1 2×106. The healthy controls were exposed to air and fed normally, the COPD model controls injected with normal saline at 0.5 mL/ on the first day of modeling by fumigation, the mice of the imDC group injected via the tail vein with 1 ×106 imDCs, and those of the DC-SOCS1 groups injected with 1 ×106 or 2 ×106 DCs with over expressed SOCS1, all via the tail vein on the 1st and 7th day of modeling. Then the lung tissues were collected from the mice for preparation of paraffin sections and HE staining, and ELISA was employed for determination of the levels of Th17-related IL-17 and IL-23 and Treg-related IL-10 and TGF-β in the BALF of the model mice.　Results　Compared with the COPD model controls, the mice in the imDC, DC-SOCS1 1×106 and DC-SOCS1 2×106 groups showed significantly decreased levels of IL-17 on the 1st day ([78.87 ± 1.08] vs [46.46 ± 0.77], [34.09 ± 3.98] and [24.12 ± 0.57] pg/mL, P < 0.05) and 7th day after modeling ([78.87 ± 1.08] vs [55.69 ±0.35], [35.65 ± 0.54] and [27.00 ± 0.58] pg/mL, P < 0.05), and IL-23 on the 1st day ([200.62 ± 0.65] vs [150.19 ± 0.53], [121.09 ± 0. 53] and [70.21 ± 0.91] pg/mL, P < 0.05) and 7th day ([200.62 ± 0.65] vs [167.70 ± 1.73], [136.34 ± 0.90] and [99.35 ± 1.83] pg/mL, P < 0.05), but remarkably increased levels of IL-10 on the 1st day ([39.46 ± 3.88] vs [50.74 ± 1.77], [58.71 ± 3.84] and [70.12 ± 2.62] pg/mL, P < 0.05) and 7th day ([39.46 ± 3.88] vs [44.56 ± 2.63], [54.78 ± 1.43] and [63.00 ± 2.57] pg/mL, P < 0.05), TGF-β on the 1st day ([24.98 ± 0.43] vs [36.46 ± 0.98], [42.40 ± 0.62] and [50.55 ± 0.53] pg/mL, P < 0.05) and 7th day ([24.98 ± 0.43] vs [33.27 ± 0.92], [40.12 ± 0.83] and [44.98 ± 0.52] pg/mL, P < 0.05). The contents of IL-17 and IL-23 were markedly lower while those of IL-10 and TGF-β higher in the DC-SOCS1 1×106 than in the imDC group (P < 0.05), and the levels of the former two significantly higher and those of the latter two lower in the DC-SOCS1 2×106 than in the DC-SOCS1 1×106 group (P < 0.05).　Conclusion　Transfusion of DCs with over-expressed SOCS1 can inhibit the secretion of Th17-related cytokines in COPD, and the effect is better than that of imDCs alone and related to the concentration and time.

Objective To understand Clonorchis sinensis infections in cats in Nanning City, so as to provide evidence for the control of the reservoir host of C. sinensis. Methods The cat livers were purchased from cat slaughterhouses in Nanning City. The cat gallbladder and liver were dissected, and liver flukes were collected and counted. Then, the worms were subjected to morphological observation, amplification of the ITS2 gene and sequencing. The species of the worms were identified using BLAST. Results A total of 105 cat livers were collected from two cat slaughterhouses, and 68 were detected with C. sinensis infections, with an infection rate of 64.76%. The highest burden was 980 worms in a single liver, and the mean burden was 72 worms in a liver. There were 3 types of liver flukes with various size and morphology, and all were identified as C. sinensis by means of morphological observation, ITS2 gene amplification, sequencing and sequence alignment. Conclusion There is a high infection rate of C. sinensi in marketed cats in Nanning City, and it is therefore suggested that targeted interventions should be intensified for the management of C. sinensis infections in cats.