Intravascular large B-cell lymphoma(IVLBCL) is a rare and aggressive type of lymphoma with diverse and nonspecific clinical manifestations, often leading to misdiagnosis. This article reports a case of IVLBCL in a middle-aged male patient who initially presented with pulmonary arterial hypertension(PAH). The patient exhibited progressive hypoxemia and PAH, showing poor response to standard PAH therapy. Laboratory tests indicated a hyperinflammatory state and significantly elevated lactate dehydrogenase levels, while imaging revealed diffuse bilateral lung lesions. Random skin biopsy identified atypical B lymphocytes within subcutaneous capillaries, confirming the diagnosis of IVLBCL. Following treatment with the ZR-CHOP regimen, the patient's symptoms and laboratory parameters improved markedly. By reviewing relevant literature, this article systematically outlines the diagnostic and therapeutic process of this case, aiming to provide insights for the clinical recognition of such rare presentations.

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.

Objective:To analyze the effect of one stitch technique of transverse incision and longitudinal suture in repairing secondary nasal deformity of cleft lip.Methods:A retrospective study was conducted on 127 patients who underwent the one stitch technique of transverse incision and longitudinal suture for repairing secondary nasal deformities after unilateral cleft lip surgery in the Department of Plastic and Aesthetic Surgery at Southern Hospital of Southern Medical University from October 2010 to December 2022. There were 58 males and 69 females with a median age of 26 (18-42) years. After removing the scar on the upper lip and the cartilage of the nasal septum during surgery, the affected nasal basal area was extensively separated. The lateral groove of the nasal wing and the tail edge of the nasal septum cartilage were sutured using one stitch technique with silk thread. Subsequently, the constricted affected nostril was enlarged by M-T flap. Outpatient follow-up visits were conducted at 1, 3, 6, 12 and 18 months after surgery. Two physicians and patients subjectively evaluated the postoperative outcomes, including very satisfied, satisfied, average, and poor, and the final evaluation results were included in statistical analysis.Results:During the treatment process, the patient did not experience any complications such as infection, hematoma, or incision rupture. A total of 116 cases were followed up for more than 3 months after surgery, of which 35.3% (41/116) were very satisfied, 38.8% (45/116) were satisfied, 24.2% (28/116) were generally satisfied, and 1.7% (2/116) were not satisfied. The two patients with poor results underwent another one stitch technique for adjustment, both achieving satisfactory results.Conclusion:The effect of one stitch technique of transverse incision and longitudinal suture for repairing cleft lip and secondary nasal deformities is stable and the satisfaction of patients is high.

Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.

OBJECTIVES: Calcium silicate (CSO) is modified to give it photothermal antibacterial properties. Its application potential in tooth mineralization and oral antibacterial is evaluated. METHODS: Based on defect-engineering modification strategy, a series of CSO-T samples (CSO-300, CSO-400, CSO-500, CSO-600) was obtained by introducing oxygen vacancy into CSO through thermal reduction using sodium borohydride. The samples were tested using scanning electron microscopy (SEM), X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet near-infrared absorption spectroscopy, and infrared thermography. The powder samples with the best photothermal performance and the most suitable material concentration (CSO-500, 500 μg/mL) were selected for subsequent experiments. High resolution transmission electron microscopy was used to analyze the microstructure and morphology of the sample, and MTT assay and Calcein AM/PI live/dead cell staining were used to evaluate the toxicity and compatibility of the sample to human oral keratinocytes. Escherichia coli and Staphylococcus aureus were selected for photothermal antibacterial experiments to evaluate their in vitro antibacterial performance. SEM, energy dispersive spectrometer, and micro Vickers hardness tester were used to evaluate the ability of materials to induce in vitro remineralization of detached teeth. RESULTS: Oxygen vacancies changed the crystal type and lattice spacing of CaSiO₃, broadened the light-absorption range, and gave it a good photothermal conversion ability in response to near infrared. Invitro experiments showed that the modified CaSiO₃ could promote the formation of hydroxyapatite on the tooth surface, thereby promoting the remineralization of teeth and improving the teeth hardness. Moreover, it had photothermal antibacterial properties and no cytotoxicity. CONCLUSIONS Defect-modified black calcium silicate has multiple functions, such as promoting tooth remineralization and photothermal bacteriostatic. When combined with the infrared luminescent toothbrush, it can simply and effectively treat tooth enamel erosion and oral bacteriostatic diseases caused by the excessive consumption of carbonated beverages and other daily bad living habits. This combination is expected to achieve the synergic treatment effect of tooth remineralization and oral bacteriostatic through daily cleaning is expected.
Calcium Compounds/pharmacology* ; Silicates/pharmacology* ; Humans ; Staphylococcus aureus/drug effects* ; Tooth Remineralization ; Escherichia coli/drug effects* ; Anti-Bacterial Agents/pharmacology* ; Keratinocytes/drug effects* ; Microscopy, Electron, Scanning

Antibiotics are chemicals with bactericidal or bacteriostatic activity produced by microorganisms and artificially synthesized. Since the discovery of penicillin by Alexander Fleming in 1928, antibiotics have been widely used in clinical treatments as well as in the animal husbandry and aquaculture, leading to antibiotic residues in soil, water, food and other environments. At the same time, antibiotic resistance is increasingly serious, which necessitates the discovery of novel antibiotics. In recent years, with the development of synthetic biology, researchers have developed a variety of whole-cell biosensors that can respond to antibiotics. These whole-cell biosensors use microbial cells to convert antibiotic signals into readable signals, which can not only perform dynamic detection of antibiotics simply, quickly, sensitively and accurately but also effectively discover novel antibiotics. This review comprehensively summarizes the reported whole-cell biosensors for antibiotics, classifies them into two types (specific and general), and elaborates on the design principles and applications of the two types of antibiotic biosensors. This review will provide reference for the construction and application of other whole-cell biosensors for antibiotics.
Biosensing Techniques/methods* ; Anti-Bacterial Agents/pharmacology*

Objective:To develop an ultrasound multi-view fusion recognition model and evaluate its clinical value in diagnosing fetal conotruncal defects (CTD).Methods:This prospective study collected cardiac ultrasound images from fetuses at 20-32 weeks of gestation undergoing prenatal ultrasound at Dongguan Maternal and Child Health Hospital between September 2022 and May 2024. The case group comprised fetuses diagnosed with CTD, while controls with normal cardiac structures were collected at a 1∶2 ratio. Both groups were divided into modeling training and validation sets at a 3∶1 ratio. One optimal standard image each from the four-chamber view, left ventricular outflow tract view, right ventricular outflow tract view, and three vessels and trachea view was included per fetus. A deep learning-based multi-view fusion recognition model was developed to differentiate normal conotruncal anatomy from CTD. Model performance was validated against post-abortion pathology or postnatal echocardiography results. SAS software was used for statistical analysis to calculate the sensitivity and specificity of three fusion models (based on positivity in any two, three, or four views, and were designated as Fusion Model 1, Fusion Model 2, and Fusion Model 3, respectively), with the optimal model determined by the maximum Youden index. Senior, intermediate, and junior prenatal sonologists independently diagnosed cases in the validation set under blinding conditions. Their diagnostic results were compared with those of the optimal model. Paired Chi-square test (Cochran's Q test) was employed to compare the differences between the diagnostic accuracy rates of sonologists at different experience levels and the sensitivity of the optimal model, thereby analyzing the auxiliary diagnostic value of the multi-view fusion recognition model. Results:The study included 88 CTD cases, excluding six cases (non-CTD diagnosed by post-abortion pathology or postnatal echocardiography or poor image quality), divided into 60 training and 22 validation cases (12 tetralogy of Fallot, four double outlet right ventricle, three transposition of great arteries, three persistent truncus arteriosus). The control group included 176 cases, excluding 15 cases (other cardiac abnormalities confirmed postnatally or poor image quality after re-evaluation), divided into 120 training and 41 validation cases. The sensitivities of Fusion Model 1, Fusion Model 2, and Fusion Mudel 3 were 0.86, 0.64, and 0.27, while their specificities were 0.76, 0.95, and 1.00, respectively. Fusion Model 1 demonstrated the highest Youden index (0.62) and was selected as optimal. Its diagnostic sensitivity showed no significant difference from senior sonologists [86% vs. 91% (20/22), Bonferroni-corrected P>0.999], but was significantly higher than intermediate [55% (12/22), Bonferroni-corrected P=0.049] and junior sonologists [32% (7/22), Bonferroni-corrected P=0.003]. Conclusion:The deep learning multi-view fusion model achieved diagnostic performance comparable to senior sonologists, demonstrating potential value in assisting CTD diagnosis, training less experienced sonologists, and supporting research and education.

Objective To investigate the role of membrane-associated tyrosine/threonine-protein ki-nase 1(PKMYT1)in glucocorticoid(GC)-induced osteoblast(OB)apoptosis,providing a theoretical basis and potential therapeutic targets for early-stage steroid-induced avascular necrosis of the femoral head(SANFH).Methods(1)Mouse calvarial osteoblastic cells(MC3T3-E1)were selected for the study.The control group was cultured in standard medium,while the experimental group was subject-ed to osteogenic induction culture,with osteogenic capacity verified by alkaline phosphatase(ALP)and Alizarin Red S(ARS)staining.Then,mouse osteoblasts(mOB)were treated with different con-centrations of GC.After that,apoptosis was detected by using Annexin V-FITC/PI double staining as-say,while cell proliferation was assessed by using Cell Counting Kit-8(CCK8).Moreover,the expres-sions of anti-apoptotic protein B-cell lymphoma/leukemia-2(BCL-2),pro-apoptotic proteins cleaved caspase-3andcleavedcaspase-9(cleavedcaspase 3/9)weredetectedbyusing Westernblotting(WB).Meanwhile,proteomic analysis was employed to identify molecules potentially regulating GC-in-duced apoptosis in mOBs.What's more,quantitative real-time PCR(qPCR)and WB were used to further analyze PKMYT1 expression.(2)mOBs were treated with PKMYT1 inhibitor GSK-1520489A of different concentrations to screen the optimal one,and all subjects were then further divided into a control,a GC,a GSK-1520489A,and a GC+GSK-1520489A group.Later,the expression of PK-MYT1 and apoptosis-related proteins BCL-2 and cleaved caspase 3/9 of all groups were detected us-ing WB,and cell viability and cytotoxicity were evaluated by CCK8 assay,with cell proliferation by using 5-ethynyl-2'-deoxyuridine(EDU)assay and apoptosis by cell live/dead staining and Annexin V-FITC/PI double staining.(3)mOBs were infected with PKMYT1 overexpression lentiviral vectors,and its efficiency was verified by using immunofluorescence,qPCR,and WB.After successful overexpres-sion of PKMYT1,all cells were divided into the control,GC,PKMYT1 overexpression(OE),and OE+GC groups,whose cell proliferation was detected by EDU assay,and apoptosis was assessed by Annexin V-FITC/PI double staining and cell live/dead staining.(4)To verify the changes in PKMYT1 expression in human osteoblasts(hOB),hOBs extracted from human femoral heads of healthy individu-als were chosen into the control group,while those from patients with hormone-induced avascular ne-crosis of the femoral head(hSANFH)were selected into the hSANFH group.Then,PKMYT1 expres-sion in both groups was detected by using qPCR and WB.Results(1)After inducing the differentia-tion of mouse calvarial osteoblastic cells(MC3T3-E1)into mature osteoblasts,under the action of GC,compared with the control group,with the increase of GC concentration,the experimental group showed increased mOB apoptosis(P<0.01)and expression of cleaved caspase 3/9(P<0.01),but de-creased cell viability(P<0.01)and expressionof apoptosis-relatedprotein BCL-2(P<0.01).More-over,according to the proteomic sequencing,significant decrease was observed in the PKMYT1 expres-sion in mature mOBs treated with GC.(2)As to treatment of mOBs with different concentrations of PKMYT1 inhibitor GSK-1520489A,with the increase of concentration,cell viability decreased and cy-totoxicity increased(P<0.001).Moreover,compared with the control group,mOBs proliferation de-creased(P<0.001)and apoptosis increased(P<0.001)in the GSK-1520489A group.Meanwhile,com-pared with the GC group,mOB proliferation decreased(P<0.05)and apoptosis increased significantly(P<0.01)in the GC+GSK-1520489A group.(3)After overexpression of PKMYT1,in comparison with the control group,mOB proliferation increased(P<0.001)but apoptosis did not increase significantly(P>0.05)in the OE group.Moreover,compared with the GC group,mOB proliferation increased(P<0.001)but apoptosis decreased(P<0.001)significantly in the OE+GC group.(4)In hOBs extracted from human femoral head tissues,qPCR and WB results showed that PKMYT1 expression of the hSANFH group was significantly lower than the control group(P<0.001).Conclusion Down regulation of PKMYT1 expression promotes GC-induced apoptosis of mOBs.Conversely,over expression of PK-MYT1 inhibits GC-induced apoptosis of mOBs.Therefore,PKMYT1 may serve as a potential target for the early treatment of SANFH.

Objective:This study aimed to evaluate the feasibility and safety of surgical intervention for patients with stage Ⅳ esophageal cancer who demonstrated tumor regression following first-line treatment.Methods:This was a descriptive case series. The inclusion criteria for surgery were as follows: (1) an initial diagnosis of stage Ⅳ esophageal cancer, i.e. cT4b or cM1; (2) the presence of residual tumor following first-line therapy deemed potentially resectable upon reassessment; and (3) sufficient organ function to tolerate surgical procedures. Clinical data were retrospectively collected for 63 patients with stage Ⅳ esophageal cancer who underwent surgery following first-line therapy at Sun Yat-sen University Cancer Center between January 2014 and December 2023. Of these patients, 12 were initially staged as IVA, and 51 as IVB. Post-treatment restaging revealed that 9 patients achieved a clinical complete response, while 3 were downstaged to stage Ⅰ, 14 to stage Ⅱ, 24 to stage Ⅲ, and 13 to stage ⅣB (with regression of distant metastatic lesions enabling curative resection). Surgical approaches included right thoracic esophagectomy ( n=55), left thoracic esophagectomy ( n=4), and transmediastinal esophagectomy ( n=4). Additionally, 7 patients required extended organ resection. Two-field lymph node dissection was performed in 49 patients, while 14 underwent three-field lymph node dissection. Postoperative management varied: 31 patients received no adjuvant therapy, 11 underwent immunochemotherapy, 8 received immunotherapy alone, 8 underwent chemotherapy, 4 received chemoradiotherapy, and 1 received combined radiotherapy and immunotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with secondary endpoints including surgical outcomes and postoperative complications. Results:All 63 patients successfully underwent surgery without intraoperative mortality. R0 resection was achieved in 58 cases (92.1%), while R1 and R2 resections were performed in 1 case (1.6%) and 4 cases (6.3%), respectively. The mean operative time was 357±135 minutes. Postoperative complications were observed in 27 cases (42.9%), with 9 cases (14.3%) classified as Clavien-Dindo grade Ⅲ or Ⅴ. One patient (1.6%) died perioperatively. The median follow-up duration was 21 months (range: 4–107 months). The median OS was 64.8 months (95% CI: 50.9–78.6 months), and the median PFS was 68.0 months (95% CI: 53.9–82.3 months). Among 24 patients with supraclavicular lymph node metastases, 6 experienced recurrence and 8 died. Of 25 patients with abdominal metastases, 3 had recurrence and subsequently died. All 4 patients with lung metastases and both patients with bone metastases experienced recurrence and death.Conclusions:Surgical intervention is a feasible and safe treatment option for selected patients with stage Ⅳ esophageal cancer who demonstrate the potential for curative resection following first-line therapy.

Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.