BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.

Objective To assess the safety of femoral artery puncture procedures guided by X-ray and ultrasound among elderly patients.Methods A total of 480 patients undergoing transcatheter interventional treatment for cardiovascular and cerebrovascular diseases through the femoral ar-tery in our hospital between January 2016 and December 2022 were enrolled in the study.Of them,326 patients receiving femoral artery puncture guided by X-ray fluoroscopy were assigned into X-ray group,while the other 154 patients guided by vascular Doppler ultrasound were into ultrasound group.With propensity score matching(PSM)in a ratio of 1∶1,finally 270 patients were included.Their general clinical data,success rate of puncture,puncture site,and incidence of vascular complications were compared between the two groups.Multivariate logistic regression analysis was used to identify the risk factors for vascular complications.Results Before PSM,there were no statistical differences in the mean distance from the skin fold to the bifurcation of the common femoral artery(2.5±1.0 cm vs 2.4±0.8 cm)or the distance from the fold to the in-guinal ligament(6.4±1.4 cm vs 6.3±1.7 cm)between the X-ray group and the ultrasound group(P＞0.05).After PSM,the X-ray group exhibited an obviously higher incidence of puncture points below the common femoral artery than the ultrasound group(14.8％vs 6.7％,P＜0.05),but no significant differences were observed in the one-time success rate of puncture or the occur-rence of vascular complications between the two groups(P＞0.05).Multivariate logistic regres-sion analysis indicated that the presences of non-common femoral artery and femoral artery calci-fication at the puncture site was independent risk factors for vascular complications(OR=8.379,95％CI:3.561-19.717;OR=3.922,95％CI:1.664-9.242).Conclusion There is no statistical disparity in safety between X-ray-versus ultrasound-guided femoral artery puncture procedures.Cli-nicians should choose appropriate puncture procedure or combine them together based on individual con-dition of patients.

Objective:To compare the differences in radiation dose and image quality between cone-beam CT (CBCT) and multi-slice spiral CT (MSCT) applied to atlantoaxial spine imaging.Methods:Head and neck phantom was scanned at 30 exposure parameter combinations using Pramerica CBCT scanner and 15 parameter combinations using Toshiba 320-row MSCT. The effective dose ( E) of CBCT was calculated based on the Monte Carlo dose estimation software PCXMC, the E value of MSCT was obtained by multiplying the dose length product (DLP) by the related factor. t-test for two independent samples or Wilcoxon rank sum test were used for comparison of radiation dose and subjective and objective image quality between two modalities. The subjective evaluation was a 5-point subjective scale using double-blind method for edge sharpness, contrast, soft tissue level, and artifacts of the images. The signal and noise in the region of interest (ROI) were measured and the contrast signal-to-noise ratio (CNR) was calculated. Results:For radiation dose, the volumetric dose index and E values of 2.9 mGy and 27.61 μSv for CBCT were lower than those of 8.8 mGy and 433.16 μSv for MSCT, and the differences were statistically significant( z=-3.05, -5.25, P<0.05). For objective evaluation of image quality, the noise and CNR were 27.74 HU and 3.69 in CBCT group, 7.84 HU and 27.1 in MSCT group. The difference between them were statistically significant( z=-5.39, -5.42, P<0.05). The overall image quality, contrast and artifact scores of the CBCT group were 3.5, 3.0 and 5 were higher than those of the MSCT group at 2.0, 2.0, and 4.0, respectively ( z=-2.32, -2.46, -3.31, P<0.05). Conclusions:Both atlantoaxial CBCT and MSCT scans provide image quality that meets diagnostic requirements. Compared to MSCT, CBCT atlantoaxial scans can effectively reduce radiation dose according to the principle of optimization of radiation protection.

Objective:To evaluate the outcome of laser coagulation under fetoscope for placental chorioangioma (CA).Methods:The clinical data of three pregnant women with giant CA treated by laser coagulation under fetoscope in Peking University Third Hospital from January 2018 to December 2020 were analyzed retrospectively. Relevant articles up to September 2022 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed, and the clinical data of all patients were retrospectively summarized. Indications and intervention effects of fetoscopic laser therapy were analyzed. Descriptive statistics was used to describe the data.Results:Thirteen patients were involved in this study including 10 cases retrieved from the databases. The average age of the pregnant women was (30.3±6.2) years old. There were 12 cases of single pregnancy and one case of twin pregnancy (monochorionic diamnionic twin pregnancy). Except for cases for which data were not available in the literatures, at the diagnosis of CA, the average gestational age was (19.9±4.5) weeks ( n=7) and the average maximum diameter of the mass was (6.1±4.1) cm ( n=6). The patients underwent fetoscopic laser therapy at an average gestational age of (25.0±2.0) weeks ( n=13) with the average maximum tumor diameter of (7.6±2.8) cm ( n=9). After treatment, the amniotic fluid volume of three cases decreased to normal. In one case, the amniotic fluid volume decreased but was still above the upper limit of the normal range. Moreover, the maximum tumor diameter decreased in four cases; the peak systolic velocity of the fetal middle cerebral artery decreased to normal in one case; fetal heart function became normal in two cases and fetal edema was relieved in one case. Among the three patients treated in our hospital, the blood supply of CA disappeared after treatment. Intrauterine fetal death occurred in two cases. The other 11 patients gave birth to live babies at the gestational age of (36.6±3.8) weeks with five through cesarean section (5/11), five through vaginal delivery (4/11) and two not reported. The birth weight of the neonates was (2 712±1 023) g and all of them survived. The gender of five neonates were reported and all were females, two of them were monochorionic diamnionic twins. No abnormality was found in the three neonates delivered in our hospital during a six-month follow-up. No abnormality was reported in the other neonates during ten days to six months of follow-up. Conclusions:Fetoscopic laser coagulation may help reduce the size of CA, decrease complications and improve pregnancy outcomes.

Objective:To identify the causative gene and observe the phenotypic characteristics of a family with isolated microphthalmia-anophthalmia-coloboma (MAC).Methods:A retrospective clinical study. One patient (proband) and 3 family members of a family with MAC visited the Henan Eye Hospital from May 2019 to May 2022 were included in the study. The patient's medical history and family history were inquired in detail, and the best corrected visual acuity (BCVA), slit lamp microscope, fundus photography, optical coherence tomography (OCT), ophthalmological B mode ultrasound and axial length (AL) measurement were performed. The peripheral venous blood of the proband, his parents and brother was collected for Trio whole-exome sequencing and pathogenic gene screening. Fluorescence quantitative Polymerase chain reaction was used to verify the suspicious variations. The clinical features of the patient's ocular and systemic also were observed.Results:The proband, male, was 3 years old at the first visit. The horizontal pendular nystagmus was detected in both eyes. Vertical elliptical microcornea and keyhole-shaped iris colobomas were detected in both eyes. The objective refraction at first visit (3 years old) was -4.00 DS/-0.50 DC×105° (OD) and -3.50 DS/-1.25 DC×80° (OS). Refraction and BCVA at 6 years old: -6.50 DS/-2.00 DC×110°→0.05 (OD) and -6.00 DS/-1.50 DC×80°→0.2 (OS). The AL at 4 years and 10 months old was 24.62 mm (OD) and 23.92 mm (OS), respectively. The AL at 5 years and 7 months old was 25.24 mm (OD) and 24.36 mm (OS), respectively. Ultrasonography shows tissue defects in both eyes. Fundus photography showed the inferior choroidal coloboma involving optic disc. OCT showed the optic disc in both eyes was abnormal with colobomas around, and the retinal neurosensory layer in colobomas area was disordered and thin; the retinoschisis was visible in the left eye. The proband's parents and siblings have normal phenotypes. Whole exome sequencing reveals a denovo heterozygous deletion of YAP1 gene: YAP1, chr11: 10280247-102100671, NM_ 001130145, loss 1 (EXON: 6-9). The results of bioinformatics analysis were pathogenic variants. Parents and siblings were of the wild type. Conclusions:Loss of heterozygosity in exons 6-9 of YAP1 gene is the pathogenic variation in this family. It can cause abnormal development of anterior segment, chorioretinal colobomas, deepening of axial myopia, even severe macular colobomas and retinoschisis.

Kaposiform lymphangiomatosis(KLA)is an aggressive subtype of generalized lymphatic anomaly. It is difficult to diagnose because of the lack of specificity of early symptoms. Moreover, there is still a lack of effective treatment, so the prognosis of this disease is generally poor, with a 5-year survival rate of 51% and an overall survival rate of only 34%. This article reviews the progress of the genetic studies related to the development of KLA and summarizes potential drug targets. A review of the literature found that the mutations potentially associated with KLA pathogenesis included NRAS gene mutations and CBL gene mutations. The signaling pathways involved were the PI3K-AKT-mTOR pathway and the RAS-MAPK-ERK pathway. Therefore, the key molecules PI3K/AKT/mTOR and RAS/MEK in the above signaling pathway may be used as targets for KLA-targeted therapy and develop specific treatments.

Kaposiform lymphangiomatosis(KLA)is an aggressive subtype of generalized lymphatic anomaly. It is difficult to diagnose because of the lack of specificity of early symptoms. Moreover, there is still a lack of effective treatment, so the prognosis of this disease is generally poor, with a 5-year survival rate of 51% and an overall survival rate of only 34%. This article reviews the progress of the genetic studies related to the development of KLA and summarizes potential drug targets. A review of the literature found that the mutations potentially associated with KLA pathogenesis included NRAS gene mutations and CBL gene mutations. The signaling pathways involved were the PI3K-AKT-mTOR pathway and the RAS-MAPK-ERK pathway. Therefore, the key molecules PI3K/AKT/mTOR and RAS/MEK in the above signaling pathway may be used as targets for KLA-targeted therapy and develop specific treatments.

Objective:To investigate the clinicopathological features and genevariation of sporadic arteriovenous malformation (AVM) in soft tissue.Methods:Eighty cases of soft tissue sporadic AVM diagnosed in Henan Provincial People′s Hospital from January 2017 to March 2022, were retrospectively collected. The relevant indicators were detected by immunohistochemistry and fluorescent quantitative PCR, and the relevant literature was reviewed.Results:There were 42 males and 38 females patients, aged from 4 to 71 years, with a mean age of 26 years.The sites of the disease included head and neck (34 cases), limbs (24 upper limbs, 17 lower limbs) and trunk (5 cases). The main clinical manifestations were characteristic pulsation, tremor, temperature rise, local pain, ulcer or repeated bleeding, and heart failure in severe cases due to long-term hemodynamic abnormalities.Color Doppler ultrasound (CDFI) can detect the high flow characteristics of AVM.Multiple cavitary vascular shadows were seen on MRI. Microscopically, the pathological tissue involved the skin appendages, deep fat and muscle tissue, in which abnormal vascular proliferation was seen, mostly scattered, the lumen was irregularly expanded, the wall thickness was different, but most of them were thick, the vascular wall was glassy and myxoid, inflammatory cell infiltration, bleeding, thrombosis and organization were visible, and calcification was rare.Clustered proliferative muscular small vessels were found around the abnormal blood vessels.No vascular endothelial cell proliferation was found in the blood vessels of the lesion. Immunohistochemistry showed that vascular endothelial cells expressed CD31, CD34 and ERG, and muscle fibers and smooth muscle tissues in the wall expressed SMA.Elastic fiber staining showed incomplete elastic layer in the wall of the malformed artery.PIK3CA gene was detected in 15 cases, and 1 case (1/15) had mutation (mutation rate 6.7%). All cases underwent surgical resection, 73 cases were followed up for 3 months to 5 years, and 15 cases recurred.Conclusions:Sporadic AVM in soft tissue is a typical lesion of vascular malformation with high flow velocity. There are abnormal arteries and clusters of proliferating small vessels.Because of the significant difference in clinical manifestation, treatment and prognosis, pathological diagnosis should be distinguished from congenital hemangioma, intramuscular hemangioma capillary type, PTEN soft tissue hamartoma and common venous malformation.Very few cases may involve PIK3CA gene mutation, suggesting that there may be abnormal PI3K signal pathway in AVM and may participate in the occurrence and development of the disease. AVM has a high recurrence rate and needs long-term follow-up.

Plasma cell leukemia (PCL) is a plasma cell proliferative disorder with strong invasiveness, rapid progression and poor prognosis. The incidence of PCL is about (0.04-0.05)/100 000 per year. According to the multiple myeloma (MM) history, PCL can be divided into primary plasma cell leukemia (PPCL) and secondary plasma cell leukemia (SPCL). PPCL accounts for about 60% of PCL, and it is in the stage of leukemia at diagnosis and has no history of MM. SPCL accounts for the remaining 40% of PCL, and mostly shows as the MM end-stage manifestation, but also can be secondary to Waldenstrom macroglobulinemia, B-cell lymphoma, chronic lymphoblastic leukemia, amyloidosis, etc. Patients who progress from MM to SPCL account for 2%-4% of all MM patients. Due to the low incidence and strong clinical heterogeneity of PCL, the evidence-based medicine about PCL is relatively lacking, this article reviews the clinical characteristics of PCL and progress in its diagnosis and treatment.

Backgrounds::GALLIUM is a global phase III study that demonstrated significant improvements in progression-free survival (PFS) for obinutuzumab plus chemotherapy (G-chemo) vs. rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). This study aimed to report the results of a subgroup of patients in China. Methods::Patients were randomized to G-chemo or R-chemo. Responders received maintenance therapy for 2 years or until disease progression. The primary endpoint was investigator (INV)-assessed PFS. Secondary endpoints included the overall response rate (ORR) and complete response rate (CRR) at the end of induction chemotherapy, overall survival (OS), and safety.Results::Overall, 58 patients with FL were randomized to the G-chemo ( n = 25) and R-chemo arms ( n = 33). The INV-assessed PFS rate at 3 years was 81.8% in the G-chemo arm, vs. 70.2% in the R-chemo arm (hazard ratio 0.35; 95% confidence interval: 0.09-1.34; P = 0.1120). The INV-assessed CRRs (without positron emission tomography [PET]) in these arms were 24.0% and 21.2%, respectively, whereas the ORRs were 80.0% and 90.9%, respectively. INV-assessed CRR-PET was 52.6% in the G-chemo, vs. 60.9% in the R-chemo. Median OS was not reached in either arm. Grade 3 to 5 adverse events were more frequent in the R-chemo arm (97.0% vs. 88.0%). Conclusions::The results of this subgroup analysis were consistent with those of the global population, and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.Trial registration::ClinicalTrials.gov, No. NCT01332968.