BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

OBJECTIVE To study the mechanism of Wenshen Tongdu Recipe in promoting the recovery of motor function in rats with spinal cord injury.METHODS A total of 144 SD rats were randomly divided into sham operation group,model group,predni-sone group,low-dose Wenshen Tongdu Recipe group,medium-dose Wenshen Tongdu Recipe group,high-dose Wenshen Tongdu Recipe group,3BDO group,and 3BDO+Wenshen Tongdu Recipe group(medium dose).The rat spinal cord injury model was estab-lished by modified Allen's method.Intervention began 1 day after modeling,and the drug was administered continuously for 14 days.During the drug administration period,the motor function of the rats in each group was evaluated by Basso-Beattie-Bresnahan(BBB)score and inclined plane test.On the 3rd,7th and 14th days after modeling,the pathological changes of the spinal cord tissues of the rats in each group were observed by HE staining;the expression levels of inflammatory factors IL-1β,IL-6,IL-4 and IL-10 in the serum of the rats in each group were detected by ELISA;the expression of Beclin 1,LC3B and p62 proteins was detected by immu-nohistochemistry;the expression of CD16 and CD206 proteins was detected by immunofluorescence staining;the expression of autoph-agy-related molecules(Beclin 1,LC3B)and Akt/mTOR pathway-related proteins in the spinal cord tissues was detected by Western blot.RESULTS Compared with the model group,the BBB score and angle of the inclined board test of rats in the medium-dose Wenshen Tongdu Recipe group were increased,and the disordered arrangement of spinal cord tissue,spinal cord vacuoles and inflam-matory infiltration were significantly improved,especially on the 14th day.Compared with the sham operation group,the expression levels of serum IL-1β and IL-6 in the model group increased(P<0.01),and the expression levels of IL-4 and IL-10 decreased(P<0.05,P<0.01);compared with the model group,the levels of IL-1β and IL-6 in the Wenshen Tongdu Recipe group were signifi-cantly decreased(P<0.01),and the levels of IL-4 and IL-10 were significantly increased(P<0.05,P<0.01);compared with the Wenshen Tongdu Recipe group,the serum IL-1β and IL-6 concentrations of mice in the 3BDO group increased(P<0.01),and the level of IL-10 decreased(P<0.05).Compared with the sham operation group,the M1/M2 ratio,P62 protein expression,p-Akt/Akt and p-mTOR/mTOR ratios in the spinal cord tissue of the rats in the model group were significantly increased(P<0.05,P<0.01),and the relative protein expression of Beclin1 was decreased(P<0.01);compared with the model group,the M1/M2 ratio,p-Akt/Akt and p-p70S6K/p70S6K ratios in the Wenshen Tongdu Recipe group were significantly decreased(P<0.01).Compared with the model group,the Beclin1 protein level in the 3BDO group was decreased,and the p-Akt/Akt and p-mTOR/mTOR ratios were increased(P<0.05,P<0.01).Compared with the Wenshen Tongdu Recipe group,the M1/M2 ratio in the 3BDO group and the 3BDO+Wen-shen Tongdu Recipe group increased(P<0.01),the positive rates of Beclin1 and LC3B proteins in the 3BDO group decreased signifi-cantly(P<0.01),and the p-p70S6K/p70S6K ratio in the 3BDO+Wenshen Tongdu Recipe group increased significantly(P<0.01).CONCLUSION Wenshen Tongdu Recipe may regulate microglial polarization through Akt/mTOR signaling pathway to acti-vate autophagy,promote the secretion of anti-inflammatory factors,reduce the release of pro-inflammatory factors,alleviate neuroin-flammatory response,and thus promote spinal cord injury repair.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Large B-cell lymphoma(LBCL),formerly known as diffuse large B-cell lymphoma(DLBCL),is the most common type of lymphoma,characterized by high invasiveness and strong heterogeneity.The World Health Organ-ization(WHO)lymphoma classification has been continually updated to better differentiate the biological behaviors of various subtypes of DLBCL.These updated classifications are increasingly important for prognosis stratification and treatment decisions for oncologists.The increasingly refined classification of DLBCL will inevitably require pathologists to make more precise diagnoses.Furthermore,the advances and growing diversity in lymphoma treatment also create a demand for precision diagnosis in LBCL,including therapy-target evaluation.Based on our own experience,we have systematically reviewed and summarized the current knowledge and progress in precision diagnosis of LBCL.This re-view aims to emphasize the importance of precision diagnosis in LBCL,help readers understand the relevant concepts more comprehensively and accurately,and promote the adoption of more reasonable diagnostic procedures.

Objective To investigate the characteristics and clinical significance of serum immunoglob-ulins in patients with Cronkhite-Canada syndrome(CCS).Methods This retrospective study included CCS patients admitted to Peking Union Medical College Hospital from December 2009 to September 2024 who under-went serum immunoglobulin testing.Clinical manifestations and ancillary examination results were analyzed ret-rospectively.Results Fifty-two patients were included(male:36[69.2%],female:16[30.8%]),with median onset age of 60(54-64)years and median diagnostic delay of 5(3-12)months.Common manifesta-tions included diarrhea(86.5%),abdominal pain(40.4%),hematochezia(19.2%),weight loss(86.5%),nail malnutrition(100.0%),pigmentation(88.5%),hair loss(84.6%),and hypogeusia(69.2%).Serum IgG reduction occurred in 21 patients(50.0%),while total IgE elevation was observed in 20(71.4%).Elevated serum IgG4 levels were noted in 11 patients(23.4%),with no significant clinical differences between IgG4-elevated and normal groups.IgG4 levels showed no statistical difference between active(n=43)and remission(n=27)groups.The hair loss rate was significantly higher in the total IgE-ele-vated group than that in the normal total IgE group(P=0.0383).Conclusions CCS patients exhibit periph-eral blood immunoglobulin disorders,with elevated IgE levels correlating with hair loss.This suggests an im-mune-mediated mechanism may underlie hair loss in CCS.

Objective To explore the relationship between the degree of compression and shape grading of the cerebral cistern ambiens in hypertensive cerebral hemorrhage(HCH)patients after neural endoscopic intracranial hematoma evacuation(NEIHE)and prognosis.Methods 246 HCH patients who underwent NEIHE surgery from January 2020 to June 2023 were selected as the research subjects.According to the postoperative 6 month Glasgow outcome score(GOS),the patients were divided into good prognosis group(n=158)and poor prognosis group(n=88).Hierarchical regression model was used to analyze the relationship between clinical pathological features and the degree of compression and shape grading of the cerebral cistern ambiens.Multivariate logistic regression model was used to analyze the independent risk factors affecting the poor prognosis of patients with HCH after NEIHE,and a prediction model was constructed.Receiver operating characteristic curve(ROC curve)was drawn with poor prognosis as the outcome variable.Area under the curve(AUC),integrated discrimination improvement(IDI)and net reclassification improvement(NRI)of different prediction models were compared.Hosmer-Lemeshow was used to test the goodness of fit.Generalized additive model(GAM)was used to analyze the relationship between GOS and related factors.Results Compared with the good prognosis group,the poor prognosis group had more preoperative blood loss,lower preoperative Glasgow coma score(GCS),and higher proportion of patients with midline deviation,hypertension history ≥10 years,hemorrhage breaking into the brain ventricle,and operation time in the late stage,the differences were statistically significant(P＜0.05).Compared with the good prognosis group,the proportions of patients with ipsilateral and contralateral cerebral cistern ambiens compression of 3 to 4 points and the morphological classification of cerebral cistern ambiens of grade V in the poor prognosis group were higher,and the differences were statistically significant(P＜0.05).The location of bleeding,midline deviation,and intracranial pressure all had an impact on the degree of compression and morphological grading of the cerebral cistern ambiens,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis(model 2:including the degree of compression and shape grading of the cerebral cistern ambiens)showed that midline deviation,history of hypertension ≥10 years,preoperative bleeding volume＞37 mL,bleeding into the brain ventricles,preoperative GCS＜7 points,late surgical timing,degree of compression of the cerebral cistern ambiens(3 to 4 points on the same side of hematoma,3 to 4 points on the opposite side of hematoma),and grade V morphology were all risk factors influencing the poor prognosis of patients with HCH after NEIHE(P＜0.05).After incorporating the degree of compression and morphological grading of the cerebral cistern ambiens into model 1(excluding the degree of compression and shape grading of the cerebral cistern ambiens),the AUC increased to 0.812(95％CI:0.763～0.872),and both the IDI(0.081,95％CI:0.049～0.095)and NRI(0.611,95％CI:0.510～0.674)of the model improved,with statistically significant differences(P＜0.05).Compared with model 1,model 2 showed an increase in AUC(0.826,95％CI:0.771～0.863),IDI(0.085,95％CI:0.052～0.110),and NRI(0.628,95％CI:0.510～0.709),with statistically significant differences(P＜0.05).The Hosmer-Lemeshow test showed that model 2(P=0.878)had a better fit for predicting poor prognosis than model 1(P=0.691).GAM analysis showed that the higher the degree of compression and morphological grading of the cerebral cistern ambiens,the lower the GOS,and the difference was statistically significant(P＜0.05).ROC curve analysis showed that the combined application of degree of compression and morphological grading of the cerebral cistern ambiens had a high predictive value for poor prognosis,with AUC of 0.935(95％CI:0.890～0.971),sensitivity of 70.26％,and specificity of 93.84％.Conclusion The degree of compression and shape changes of the cerebral cistern ambiens in HCH patients after NEIHE are closely related to prognosis,and the combined application has certain predictive value for poor prognosis.The location of bleeding,midline deviation,intracranial pressure,and other factors significantly affect the compression degree and shape change of the cerebral cistern ambiens.

Objective:To evaluate the clinical efficacy of the Masquelet technique (induced membrane technique) combined with an antibiotic-impregnated bone cement-coated plate for the treatment of infected nonunion following internal fixation of clavicle fractures.Methods:A retrospective analysis was conducted on 12 patients with clavicular infected nonunion who underwent staged treatment using the Masquelet technique combined with an antibiotic-loaded bone cement-coated plate between May 2021 and May 2023 in the Second Ward of Traumatic Orthopedics at Gansu Provincial People's Hospital. The cohort included 8 males and 4 females, with a mean age of 28.8±3.1 years (range: 12-48 years). Among them, 10 cases had mid-third clavicular defects, and 2 cases had lateral third defects. All 12 cases involved nonunion due to bone infection following internal fixation of clavicle fractures, with 6 cases initially fixed with Kirschner wires and 6 with plates. The induced membrane technique was applied in two stages. Stage One: Radical debridement was performed, including removal of the original internal fixation and infected necrotic tissue. A plate was implanted, and the bone defect area was filled with antibiotic-loaded bone cement, fully encapsulating the plate. Stage Two: Bone graft reconstruction was carried out 6-8 weeks later, after infection control was confirmed. The induced membrane was incised, the bone cement was removed, and a bone graft was placed within the membrane. Outcomes included infection control, bone union time, pain visual analogue scale (VAS), and Constant-Murley shoulder score (CMS) at the final follow-up.Results:The interval between the first and second surgeries was 7.42±1.17 weeks (range: 6-10 weeks). All 12 patients were followed up for a mean duration of 16.4±3.9 months (range: 12-24 months). One patient experienced recurrent infection after the first-stage surgery, which was controlled after repeat debridement and replacement of antibiotic-loaded bone cement, with no recurrence during follow-up. All 12 patients achieved bony union, with a mean healing time of 3.42±0.67 months (range: 3-5 months). Radiographs showed continuous bone cortex with no visible fracture lines. At the final follow-up, the mean VAS score was 0.42±0.51, significantly lower than the preoperative score of 6.68±1.12 ( t=18.711, P<0.001). The mean CMS score was 88.93±3.94, significantly higher than the preoperative score of 44.41±7.15 ( t=20.786, P<0.001). Conclusion:The Masquelet technique combined with an antibiotic-loaded bone cement-coated plate is effective in treating infected nonunion after internal fixation of clavicle fractures, significantly improving acromioclavicular joint function.

Objective:To explore the values of reticulin fiber staining (RFS) in evaluating bone marrow (BM) involvement of lymphoma and in grading of BM biopsy from adult lymphoma patients.Methods:Retrospectively,354 cases of adult lymphoma were collected from November 2023 to May 2024 at Peking University Cancer Hospital. BM samples were stained with RFS and immunohistochemical staining (IHC), and flow cytometry (FCM) was also performed with the BM aspirations simultaneously. RFS was graded according to the European Consensus, as high grade (grade 2-3) indicating BM involvement in the study. BM involvement was considered as definite if no less than two positive findings among IHC, FCM, and RFS. Statistical analyses were performed via SPSS software (V23.0).Results:In this series, 52.3% (185/354) of the patients were male; 35.0% (124/354) aged >60 years; BM involvements were found in 34.5% (122/354) cases with high grade of RFS, which, in turn, were lymphoblastic leukemia/lymphoma (ALL/LBL) group (4/4), indolent B-cell lymphoma (IndBCL) group (49.1%, 53/108), transformed B-cell lymphoma (TrBCL) group (2/5), invasive B-cell lymphoma (InvBCL) group (26.5%, 41/155), T and NK cell lymphoma (TNKCL) group (27.3%, 12/44) and classical Hodgkin lymphoma (CHL) group (26.3%, 10/38); if classified by specific types, T-ALL/LBL (2/2), B-ALL/LBL (2/2) and CLL/SLL (8/10) ranked top three. In terms of the positive rate of BM involvement evaluated by RFS, no significant difference was seen between either gender or age groups ( χ2=3.416, P=0.332 and χ2=4.200, P=0.241); however, significant differences were observed between different lymphoma groups and types ( χ2=29.961, P=0.012 and χ2=102.546, P<0.001, respectively). BM invasion rates indicated by IHC and FCM were 25.4% (90/354) and 13.8% (49/354), respectively. The overall BM invasion rate was 24.3% (86/354), and the sensitivity of RFS, IHC, and FCM was 90.8%, 97.8%, and 55.8%, and specificity was 84.1%, 99.6%, and 98.9%, respectively. Overall, the concordance rate of RFS with IHC and FCM was 83.6% and 74.0%, respectively, including 85.8% and 74.2% for InvBCL group, 79.6% and 75.0% for IndBCL group, 84.1% and 75.0% for TNKCL group, 81.6% and 73.7% for CHL group, 5/5 and 2/5 for TrBCL group, and 4/4 and 3/4 for ALL/LBL group. Conclusions:In the evaluation of BM involvement status of adult lymphoma, high sensitivity and specificity are observed by RFS, and high concordance is also noted with both IHC and FCM. Thus, the BM infiltrating status of adult lymphoma could be evaluated more accurately by a combined usage of the three methods.