Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Objective:To investigate the differences in gene expression levels in knee chondrocytes and chondrons in vitro.Methods:The chondrocytes and chondrons were isolated from full thickness of the 8-months ( n=5) rabbit knees cartilage. Chondrons from right knee were enzymatically isolated using 0.3% dispase and 0.2% collagenase-2 with shaking for 3 hours. Chondrocytes were isolated by 0.4% Pronase and 0.025% collagenase-2 from left knee. The mRNA levels in chondrocytes and chondrons were analyzed by quantitative real-time PCR, including matrix proteins [aggrecan(Agg), collagen(Col-2), Col-6A6, Col-10, Col-11], MMPs and inhibitors (MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3), cytoskeletal proteins (Sox-9, vinculin, tubulin, actin), cytokines (IL-β, TNF-α). Analysis was performed using SPSS 16.0 statistical software, and the two-group comparisons were considered as significant by t-test at P<0.05. Results:Compared to the chondrocytes, the Agg [(5.78±0.90) vs (1.89±0.27), t=9.26, P<0.001], Col-2 [(6.29±0.76) vs (3.06±0.60), t=7.46, P<0.001], Col-6A6 [(0.89±0.18) vs (0.22±0.06), t=7.90, P<0.001], Col-10 [(3.83±0.76) vs (1.00±0.26), t=7.88, P<0.001] and TIMP-1 [(1.98±0.85) vs (1.03±0.34), t=2.32, P=0.049], TIMP-2[(3.46±1.50) vs (1.52±1.06), t=2.36, P=0.046], TIMP-3 [(3.96±0.50) vs (1.36±0.18), t=10.94, P<0.001], Sox-9 [(7.09±2.93) vs (3.24±0.77), t=2.84, P=0.022], vinculin [(3.42±1.69) vs (1.46±0.68), t=2.41, P=0.043], tubulin[(9.34±0.71) vs (2.35±0.80), t=14.61, P<0.001] showed higher expression in the chondrons. Compared to the chondrocytes, the MMP-1 [(1.02±0.30) vs (2.67±0.45), t=6.91, P<0.001], MMP-3 [(1.21±0.32) vs (2.52±0.79), t=3.44, P=0.009], MMP-13 [(1.23±0.34) vs (3.42±0.86), t=5.30, P=0.007], IL-1β [(1.02±0.14) vs (2.70±0.49), t=7.37, P<0.001], TNF-α [(0.99±0.08) vs (3.15±0.54), t=8.85, P<0.001] showed lower expression in the chondrons. There were no difference between chondrons and chondrocytes for Col-11, MMP-9, actin ( P>0.05). Conclusion:The gene expression of extracellular matrix components are higher and the gene expression levels of inflammatory factors and MMPs are decreased in chondrons compared with the chondrocytes, suggesting the chondrons have more multiplication potential as seeding cells for tissue-engineered cartilage.

Objective:To investigate the effect of HNRNPL protein on the proliferative ability of primary hepatocellular carcinoma cells and its potential mechanism.Methods:Online public database and real-time quantitative PCR were used to analyze the difference of HNRNPL expression between cancer and adjacent tissues. The effects of HNRNPL on HCC cell MHCC97H and HepG2 proliferation and MAPK pathway were investigated by Western blot, cell counting assay, colony formation assay and nude mouse transplantation tumor experiments.Results:The level of HNRNPL mRNA was validated to be higher in HCC tissue (2.76±0.37) than in normal tissue (1.00±0.14) with statistical difference ( t=3.93, P=0.002). Colony formation assay showed that the colony numbers of two MHCC97H knockdown groups (33.3±7.7) and (43.3±2.2) were lower than their control group (84.3±6.2), and two HepG2 knockdown groups (59.0±15.5) and (41.7±4.8) were lower than their control group (200.3±6.2) with statistical difference (both P<0.01). HNRNPL knockdown decreased the proliferation ability and activation level of MAPK pathway in HCC cells. Overexpression of oncogene c-RAF partially alleviated the anti-proliferation effect of HNRNPL knockdown and rescued the tumorigenic capacity. Conclusion:HNRNPL can promote hepatocellular carcinoma cell proliferation by activating MAPK signaling pathway.

Objective To investigate the pattern of nodal recurrence after curative resection in adenocarcinoma of the gastroesophageal junction ( AGE ) , and to provide a basis for delineation of the radiation range in the high-risk lymphatic drainage area.Methods A retrospective analysis was performed in 78 patients with locally advanced AGE who were newly treated in our hospital from January 2009 to December 2013 and had complete clinical data.All patients received curative resection and were pathologically diagnosed with stage T3/T4 or N (+) AGE.Those patients were also diagnosed with SiewertⅡor Ⅲ AGE by endoscopy, upper gastroenterography, macroscopic examination during operation, and pathological specimens.None of the patients received preoperative or postoperative radiotherapy.All patients were diagnosed by imaging with postoperative nodal recurrence.The computed tomography images of those
patients were accessible and had all the recurrence sites clearly and fully displayed.Results The median time to recurrence was 10 months ( 1-48 months) , and 90%of the recurrence occurred within 2 years after surgery.The lymph nodes with the highest risk of recurrence were No.16b1( 39%) , No.16a2( 37%) , No.9 (30%), and No.11p (26%), respectively.There was no significant difference in the recurrence rate within each lymphatic drainage area between patients with SiewertⅡandⅢAGE ( P=0.090-1.000) .The lymph nodes with the most frequent recurrence were No.16b1, No.16a2, No.9, No.16b2, No.11p, and No.7 in patients with stage N3 AGE and No.11p, No.16b1, No.16a2, No.9, No.8, and No.7 in patients with stage non-N3 AGE.Patients with stage N3 AGE had a significantly higher recurrence rate in the para-aortic regions (No.16a2-b2) than those with stage non-N3 AGE (67%vs.33%, P=0.004, OR=4.00, 95% CI=1.54-10.37) .Conclusions The lymph nodes with the highest risk of recurrence are located in the celiac artery, proximal splenic artery, and retroperitoneal areas ( No.16a2 and No.16b1) in patients with SiewertⅡorⅢlocally advanced AEG.Moreover, patients with stage N3 AGE have a higher risk of retroperitoneal recurrence.The above areas should be involved in target volume delineation for postoperative radiotherapy.

OBJECTIVETo photoelastically investigate the difference in load distribution of Tension More (TM) implants with different conical angle designs.

METHODSThe following five groups of implants of different conical angles were designed: cylinder implant, upper 1/3 TM implant (taper length of 3 mm); 1/2 TM implant (taper length of 5 mm); lower 1/3 TM implant (taper length of 7 mm); and bottom TM implant (taper length of 10 mm). The implants were centrally located in individually photoelastic models consisting of a simulated trabecular bone and a 1 mm-thick layer of cortical bone. Vertical and 45° oblique static loads were applied at the center of the superstructures. The resulting stresses were monitored photoelastically and recorded photographically. RESULTS With vertical loading, the cylinder implant showed higher stress levels in the cortical bone and trabecular bone than the upper 1/3 TM implant, 1/2 TM implant, and lower 1/3 TM implant. The four groups of TM implants showed lower stress levels in the cortical bone than the cylinder implant under oblique loads. The least favorable stress concentration in cortical bone was observed in the upper 1/3 TM implant under vertical and oblique loads.

CONCLUSIONTM implants of rational conical angle designs seem to be effective in stress distribution. For all designs and load directions, the upper 1/3 TM implant is the most favorable around the crest.

Bone and Bones ; Dental Implants ; Stress, Mechanical

Objective To photoelastically investigate the difference in load distribution of Tension More (TM) implants with different conical angle designs. Methods The following five groups of implants of different conical angles were designed: cylinder implant, upper 1/3 TM implant (taper length of 3 mm); 1/2 TM implant (taper length of 5 mm); lower 1/3 TM implant (taper length of 7 mm); and bottom TM implant (taper length of 10 mm). The implants were centrally located in individually photoelastic models consisting of a simulated trabecular bone and a 1 mm-thick layer of cortical bone. Vertical and 45° oblique static loads were applied at the center of the superstructures. The resulting stresses were monitored photoelastically and recorded photographically. Results With vertical loading, the cylinder implant showed higher stress levels in the cortical bone and trabecular bone than the upper 1/3 TM implant, 1/2 TM implant, and lower 1/3 TM implant. The four groups of TM implants showed lower stress levels in the cortical bone than the cylinder implant under oblique loads. The least favorable stress concentration in cortical bone was observed in the upper 1/3 TM implant under vertical and oblique loads. Conclusion TM implants of rational conical angle designs seem to be effective in stress distribution. For all designs and load directions, the upper 1/3 TM implant is the most favorable around the crest.

OBJECTIVETo study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation.

METHODSTissue specimens from 3 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed.

RESULTSThe typical pathological changes of lungs were diffuse hemorrhaging on the surface. A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro-thrombosis in some of these capillaries. Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline-membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces. There were thromboembolisms in some bronchial arteries. Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas.

CONCLUSIONSevere damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients.

Aged ; Humans ; Lung ; pathology ; Lymph Nodes ; pathology ; Male ; Middle Aged ; Severe Acute Respiratory Syndrome ; pathology ; Spleen ; pathology