Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

Objective:To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML).Methods:A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology,Affiliated Hospital of Jinggangshan University from January 2020 to December 2022.Among them,26 patients received venetoclax combined with azacitidine chemotherapy(observation group),and 22 patients received daunorubicin plus cytarabine chemotherapy(control group).The differences in complete response(CR)rate,objective response rate(ORR),progression-free survival(PFS),overall survival(OS)and adverse reactions(AR)were compared between the two groups.Results:There was no significant difference in age,sex ratio,absolute value of tri-lineage cell and proportion of bone marrow primordial cells between the two groups before treatment(all P＞0.05).The CR rate and the ORR rate of the observation group was significantly higher than that of the control group(P＜0.05).After treatment,there were no significant difference in the adverse reactions such as myelosuppression,granulocytosis,secondary infection,mucosal damage,liver and kidney damage,cardiotoxicity and gastrointestinal toxicity between the two groups(P＞0.05).The median PFS and the median OS of the observation group were significantly better than those of the control group(P＜0.05).Conclusion:The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia.Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Objective To investigate the effect of Polyetheretherketone(PEEK)rod semi-rigid pedicle screw fixation sys-tem in lumbar spine non-fusion surgery.Methods A total of 74 patients with tow-level lumbar degenerative diseases who un-derwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group.In the PEEK rod group,there were 34 patients,including 13 males and 21 females,aged from 51 to 79 years old with an average of(62.4±6.8)years old;There were 1 patient of L1-L3 segments,7 patients of L2-L4 segments,20 patients of L3-L5 segments and 6 pa-tients of L4-S1 segments.In the titanium rod group,there were 40 patients,including 17 males and 23 females,aged from 52 to 81 years old with an average of(65.2±7.3)years old;There were 3 patient of L1-L3 segments,11 patients of L2-L4 segments,19 patients of L3-L5 segments and 7 patients of L4-S1 segments.The general conditions of operation,such as operation time,intraoperative blood loss,postoperative drainage was recorded.The visual analogue scale(VAS)for low back pain and Os-westry disability index(ODI)were compared in preoperatively and postoperatively(3 months,12 months and last follow-up)between two groups.The change of range of motion(ROM)was observed by flexion and extension x-ray of lumbar Results All patients successfully completed the operation.The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6)months.The operative time(142.2±44.7)min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group[(160.7±57.3)min、(212.8±85.4)ml](P＜0.05).There was no significant differences in postoperative drainage between the two groups(P＞0.05).At the final follow-up visit,in PEEK group and titanium group VAS of low back pain[(0.8±0.4)points vs(1.0±0.5)points],VAS for leg pain[(0.7±0.4)points vs(0.8±0.5)points]and ODI[(9.8±1.6)％vs(12.1±1.5)％]were compared with preoperative[(5.8±1.1)points vs(6.0±1.1)points],[(7.2±1.7)points vs(7.0±1.6)points],[(68.5±8.9)％vs(66.3±8.2)％]were significantly different(P＜0.05).There was no significant difference in VAS scores between the two groups at each postoperative time point(P＞0.05).At 3 months after surgery,there was no difference in ODI between the two groups(P＞0.05).There were significant differences in ODI between PEEK group and titanium rod group at 12 months[(15.5±2.1)％vs(18.4±2.4)％]and at the last follow-up[(9.8±1.6)％vs(12.1±1.5)％](P＜0.05).The total range of motion(ROM)of lumbar decreased in both groups after surgery.At 12 months after surgery and the last follow-up,the PEEK group compared with the titanium rod group,the total range of motion of lumbar was statistically significant(P＜0.05).The range of motion(ROM)of the fixed segments decreased in both groups after surgery.The ROM of the fixed segments in PEEK group decreased from(9.5±4.6)° to(4.1±1.9)° at the last follow-up(P＜0.05),which in the titanium rod group was de-creased from(9.8±4.3)°to(0.9±0.5)° at the last follow-up(P＜0.05).The range of motion(ROM)of upper adjacent segment increased in both groups,there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up,(P＜0.05).There was no screw loosening and broken rods in both groups during the follow-up period.Conclusion The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment,showing comparable short-term clinical efficacy to titanium rod fu-sion.PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degener-ative diseases,and its long-term efficacy needs further follow-up observation.

In industrial production,the expression level of drug proteins in Chinese hamster ovary cells(CHO)is influenced by many factors:the regulatory elements on transcription and translation,the ge-nomic integration sites,and the expression system.Transcription,as the first step of gene expression,largely affects protein expression,and the promoter plays a crucial role in the initiation of transcription.Most of the promoters were screened through transient transfection or random integration,but the presence of unclear copy number or random integration sites makes it difficult to accurately evaluate the promoter activity.To some extent,site-specific integration can reduce the impact of positional effects on exogenous genes and may potentially increase the expression level of exogenous genes.In the early stage of our re-search,multiple sites that can stably express exogenous proteins were identified and verified in the CHO cell genome.In this study,one of these sites(2c6)was selected for the evaluation of promoter activity.The CRISPR/Cas9 gene editing technique was used to site-specifically integrate the reporter gene(EG-FP)regulated by the simian virus early promoter(SV40),mouse elongation factor-1α(mEF-1α),chicken β-actin(cACTB)promoter,and human phosphoglycerate kinase promoter(hPGK)into the 2c6 site,respectively.The mean fluorescence intensity of the cells was analyzed by flow cytometry,and the mRNA level of EGFP was detected by qPCR to comprehensively evaluate the activity of the promoter.The results showed that the activities of the mEF-1α and mACTB promoters were better than those of SV40 and hPGK.The results of the secondary flow cytometry sorting showed that site-specific integration can more accurately evaluate the activity of the promoter in the CHO cell expression system.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to rapidly identify the chemical components in Dracocephalum moldavica, and UPLC was employed to determine the content of its main components. MS analysis was performed using an electrospray ionization(ESI) source and data were collected in the negative ion mode. By comparing the retention time and mass spectra of reference compounds, and using a self-built compound database and the PubChem database, 68 compounds were identified from D. moldavica, including 36 flavonoids, 22 phenylpropanoids, 4 phenols, and 6 other compounds. On this basis, a UPLC quantitative method was established to simultaneously determine 8 main components, i.e., luteolin-7-O-glucuronide, apigenin-7-O-glucuronide, rosmarinic acid, diosmetin-7-O-glucuronide, tilianin, acacetin-7-O-glucuronide, acacetin-7-O-(6″-O-malonyl)-glucoside, and acacetin. A Waters ACQUITY BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm) was used, with acetonitrile and a water solution containing 0.1% formic acid and 0.1% phosphoric acid as the mobile phase for gradient elution. The detection wavelength was set at 330 nm, with a flow rate of 0.4 mL·min~(-1), and the column temperature was maintained at 35 ℃. The 8 components demonstrated good linearity(r≥0.999 9) over a wide mass concentration range(50 or 100 times). The average recovery rate ranged from 97.5% to 105.1%, and the relative standard deviations(RSDs) were 0.90% to 3.4%(n= 6), indicating that the method was simple, accurate, and reliable. In 17 batches of D. moldavica samples, the content of these 8 components ranged from 0.405 to 2.10, 0.063 to 0.342, 0.446 to 2.43, 0.415 to 1.47, 1.57 to 4.34, 0.173 to 0.386, 1.00 to 5.40, and 0.069 to 0.207 mg·g~(-1), respectively. These results indicate significant differences in the internal quality of the samples, highlighting the need for strict quality control to ensure their pharmacodynamic efficacy. This study provides a scientific basis for the rapid discovery of pharmacodynamic substances, comprehensive quality control, and the formulation or revision of quality standards for D. moldavica.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Lamiaceae/chemistry* ; Flavonoids/chemistry*

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

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*