This report describes two cases of severe immune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with umbilical cord mesenchymal stem cells (UC-MSCs). Case 1 was a child with severe aplastic anemia who underwent haploidentical bone marrow and peripheral blood HSCT, with a chimerism rate of 99.8% on day +25 and severe immune-mediated thrombocytopenia on day +60. After intravenous immunoglobulin (IVIG) pulse therapy, platelet count increased temporarily but then decreased, while cyclosporine, methylprednisolone, and rituximab had a poor therapeutic effect. Case 2 was a child with Gaucher's disease who underwent unrelated umbilical cord blood HSCT, with a chimerism rate of 96.35% on day +41 and severe immune-mediated thrombocytopenia on day +153. After three sessions of IVIG pulse therapy, the platelet count increased initially but subsequently decreased. Therapies with dexamethasone, prednisone, cyclosporine, and recombinant human thrombopoietin also yielded a poor response. Both children received three sessions of UC-MSCs infusion, and platelet counts increased and were subsequently maintained within the normal range. Case 1 has been followed up for 10 years and remains in disease-free survival. UC-MSCs infusion may be effective for severe immune-mediated thrombocytopenia that is unresponsive to first- and second-line therapies after HSCT and could potentially improve the quality of life and disease-free survival rate.
Child ; Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Thrombocytopenia/therapy* ; Transplantation, Homologous ; Umbilical Cord/cytology*

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Objective:To investigate the diagnostic efficacy between magnetic resonance imaging(MRI)and ultrasound for training injury of medial head of gastrocnemius muscle.Methods:Clinical data of 70 cases with lower limb training injury suspected to be in the medial head of gastrocnemius muscle from Jan 2013 to Jan 2022 were retrospectively analyzed.All patients were examined by ultrasound and MRI,and their sensitivity,specificity and accuracy according to the final clinical diagnosis was compared.Results:Of the 70 cases of training injury,48 cases were finally diagnosed as medial head injury of gastrocnemius muscle,and 22 cases had no gastrocnemius injury.And there were 19 cases of gastrocnemius tissue injury,28 cases of myofascial injury edema and tissue interstitial effusion,26 cases of tendon and tendon sheath injury,and 6 cases of tendon insertion enthesiopathy.The sensitivity of ultrasound and MRI in the diagnosis of training injury of medial head of gastrocnemius muscle were 85.4%(41/48),97.9%(47/48)and the accuracy was 84.3%(59/70),95.7%(67/70),respectively.The diagnostic accuracy and sensitivity of MRI were higher than those of ultrasound(P＜0.05).There was no significant difference in specificity between the two methods(P＞0.05).Conclusion:MRI has higher accuracy and sensitivity compared with ultrasound in the diagnosis training injury of medial head of gastrocnemius muscle,which has important diagnostic value.

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy ; Cell Proliferation ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism*

Objective:To explore the quality differences of systemic biopsy specimens from different regions in prostate biopsy.Methods:The data of 806 patients who underwent transperineal prostate biopsy from May 2013 to December 2020 in Northern Jiangsu People’s Hospital were retrospectively reviewed. The median age of the patients was 72 (66, 77) years old, median PSA was 18.4 (10.3, 34.2) ng/ml, and prostate volume was 43 (32, 56) ml. Tissue quality were graded from low to high as follows. One score means multiple fragments with fragmented tissue ≤5 mm. Two scores means at least one fragment >5 mm and ≤10 mm. Three scores means at least one fragment >10 mm. The prostate specimens fragmentation scores and the length of the specimens in different regions of the prostate were collected to analyze.Results:A total of 806 patients were included in our study. The number of tissues was 8 866, and the mean length of tissues was 1.2 (1.0, 1.5) cm. The tissues of different region were scored according to the scoring criteria, of which 618 (7.0%) prostate tissues were scored as 1 score, 2 720 (30.7%) tissues were scored as 2 scores, and 5 528 (62.4%) tissues were scored as 3 scores. In the prostate apex, tissue quality of 1 score accounted for 11.7%(94/806), 2 scores accounted for 34.7%(280/806), and 3 scores accounted for 53.6%(432/806). While in the prostate base, tissue quality of 1 score accounted for 6.5%(524/8 060), 2 scores accounted for 30.3%(2 449/8 060), and 3 scores accounted for 63.2%(5 096/8 060)( H=35.850, P<0.05). The mean length of the prostate apical tissue was 1.0 (0.8, 1.3) cm, which was significantly shorter than prostate basal tissue of 1.2(1.0, 1.5) cm ( Z=-11.353, P<0.05). Conclusions:In transperineal prostate biopsy, the apical tissue was more fragmented and shorter, prostate apex should be concerned.

Biomarkers, Tumor ; DNA Helicases ; Humans ; Neoplasms ; Nuclear Proteins/genetics* ; Transcription Factors

Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.
Biomarkers, Tumor/genetics* ; Carcinoma/pathology* ; China ; DNA Helicases ; Female ; Gastrointestinal Tract/pathology* ; Humans ; Keratins ; Male ; Nuclear Proteins ; Retrospective Studies ; Transcription Factors

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

OBJECTIVE: To compare the effect among ultrasound-guided electroacupuncture (EA) at suprahyoid muscle group, conventional acupuncture and conventional EA at suprahyoid muscle group on pharyngeal dysphagia after stroke, and to explore its biomechanical mechanism. METHODS: A total of 120 patients with pharyngeal dysphagia after stroke were randomly divided into an observation group, a control-1 group and a control-2 group, 40 cases in each group. The patients in the observation group were treated with ultrasound-guided EA at suprahyoid muscle group; the patients in the control-1 group were treated with EA at Lianquan (CV 23), Wangu (GB 12) and Fengchi (GB 20), etc.; the patients in the control-2 group were treated with EA at suprahyoid muscle group according to anatomical location. The EA in the three groups were discontinuous wave, with frequency of 5 Hz and current intensity of 1 mA. The EA was given for 30 minutes, once a day, 6 times were taken as a course of treatment, and 4 courses of treatment were provided. The video floroscopic swallowing study (VFSS) was performed before and after treatment. The Rosenbek penetration-aspiration scale (PAS) score, the forward and upward movement distance of hyoid bone and thyroid cartilage, Ichiro Fujima ingestion-swallowing function score were recorded in the three groups, and the incidences of subcutaneous hematoma were recorded after treatment. RESULTS: Compared before treatment, the PAS scores were reduced and the Ichiro Fujima ingestion-swallowing function scores were increased after treatment in the three groups (P<0.05); the PAS scores in the observation group were lower than those in the control-1 group and the control-2 group, and the Ichiro Fujima ingestion-swallowing function scores in the observation group were higher than those in the control-1 group and the control-2 group (P<0.05). After treatment, the forward and upward movement distance of hyoid bone and thyroid cartilage in the observation group and the control-2 group was increased (P<0.05), and the forward and upward movement distance of hyoid bone was increased in the control-1 group (P<0.05); the forward and upward movement distance of hyoid bone and thyroid cartilage in the observation group was longer than that in the control-1 group and the control-2 group (P<0.05). The incidence of subcutaneous hematoma in the observation group was 0% (0/40), which was lower than 20.0% (8/40) in the control-1 group and 47.5% (19/40) in the control-2 group (P<0.05). CONCLUSION Ultrasound-guided EA at suprahyoid muscle group could improve the swallowing function in patients with pharyngeal dysphagia after stroke by increasing the motion of hyoid laryngeal complex. Its effect and safety are better than conventional acupuncture and conventional EA at suprahyoid muscle group.
Deglutition Disorders/therapy* ; Electroacupuncture ; Humans ; Muscles ; Stroke/diagnostic imaging* ; Ultrasonography, Interventional/adverse effects*