Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveTo analyze the characteristics of 150 patients with spinal cord injury complicated with spasticity. MethodsA cross-sectional survey was conducted on 150 patients with spinal cord injury accompanied by spasticity from September, 2019 to December, 2024. Their age, gender, cause of injury, injury site, severity of injury, spasticity severity and other indicators were recorded. The relationships between different characteristics were analyzed, and a correlation analysis of disease duration, spasticity grade, injury level, injury severity and age were conducted. ResultsThere was no significant difference in age distribution between patients with tetraplegia and paraplegia (Z = 0.806, P = 0.420). The proportions of trauma (χ² = 3.982, P = 0.046) and tetraplegia (χ² = 10.559, P = 0.010) were higher in males than in females. Trauma was the main cause of injury in both tetraplegia and paraplegia patients; the proportion of tetraplegia was higher than paraplegia in trauma patients, while paraplegia was higher than tetraplegia in non-trauma patients (χ² = 11.885, P < 0.001). Patients with tetraplegia was dominated by incomplete injury, whereas patients with paraplegia was dominated by complete injury (χ² = 10.885, P = 0.012). Grade A injury was predominant in trauma patients (P = 0.003). Spasticity grade showed a very weak positive correlation with disease duration (r = 0.175, P = 0.032) and age (r = 0.168, P = 0.040). Injury severity showed a very weak positive correlation with age (r = 0.183, P = 0.025). ConclusionCharacteristics of patients with spinal cord injury complicated with spasticity is different with gender, cause of injury, injury level, injury severity.

ObjectiveTo explore the incidence of major low anterior resection syndrome （LARS） within six months after sphincter-preserving surgery for rectal cancer and to analyze its associated factors. MethodsClinical records， postoperative rehabilitation data and LARS scores were collected from 889 patients at 3 months postoperatively and from 844 patients at 6 months postoperatively. Patients were divided into a major LARS group and a non-major LARS group. Multivariable Logistic regression was used to analyze factors associated with major LARS at 3 and 6 months postoperatively， and the predictive value of the models was assessed using the Hosmer-Lemeshow goodness-of-fit test and the receiver operating characteristic （ROC）. ResultsAmong patients undergoing sphincter-preserving surgery for rectal cancer， 247 patients （27.8%） had major LARS at 3 months postoperatively and 181 patients （21.4%） at 6 months postoperatively. Multivariable Logistic regression showed that Kegel exercises， preoperative radiotherapy， anastomotic leakage， a tumor distance from the anal verge of ≤5 cm， and an anastomotic distance from the anal verge of ≤5 cm were independent factors for major LARS at 3 months postoperatively （P<0.05）. At 6 months postoperatively， occasional Kegel exercises during 0~3 months， Kegel exercises during 4~6 months， hydrotherapy during 4~6 months， preoperative chemotherapy， a tumor distance from the anal verge of ≤5 cm， and an anastomotic distance from the anal verge of ≤5 cm were independent factors （P<0.05）. The models at 3 and 6 months postoperatively showed goodness-of-fit test P values of 0.986 and 0.517 and area under the curve （AUCs） of 0.843 and 0.870， indicating good predictive value. ConclusionThe incidence of major LARS within six months after sphincter-preserving surgery for rectal cancer is relatively high， and greater attention should be paid to patients who receive preoperative chemoradiotherapy， develop anastomotic leakage， or have tumor and anastomotic distances from the anal verge of ≤5 cm. Patients should also be advised that early postoperative Kegel exercises and hydrotherapy may reduce the incidence of major LARS.

Uncaria rhynchophylla (Miq.)Miq. ex Havil (Gouteng) is a dry and hooked stem branch of Rubiaceae, which contains chemical components including alkaloids, terpenoids, flavonoids and organic acids. It has antioxidant, anti-inflammatory, and potential therapeutic effects on various diseases. The characteristics of network pharmacology are multi-component, multi-target and multi-channel, which can analyze the complex mechanism of the active ingredient group of traditional Chinese medicine and the disease markers, and clarify the relationship between drugs, targets and diseases. This review summarises the research progress of the intervention of Gouteng in neurological disorders, cardiovascular diseases, inflammation, and other diseases based on network pharmacology and provides a theoretical foundation for the clinical application of Gouteng.

Objective: To retrospectively analyze the clinical data of 474 newborns with hyperbilirubinemia, and to investigate the clinical characteristics of hyperbilirubinemia caused by ABO hemolytic disease of the fetus and newborn (ABO-HDFN) and factors influencing the phototherapy duration. Methods: A total of 474 neonates with hyperbilirubinemia treated in the First Hospital of Lanzhou University from January 2019 to January 2023 were enrolled. Blood type identification and the standard serological tests (direct antiglobulin test, serum free antibody test, and antibody elution test) were performed for all neonates. Baseline clinical data were collected and analyzed. According to the results of the hemolysis tests, neonates were divided into hemolytic jaundice group and non-hemolytic jaundice group. Clinical indicators, including hemoglobin levels, length of hospital stay, and phototherapy duration, were compared between the two groups. A multiple linear regression model was used to explore clinical factors influencing the duration of phototherapy. Results: Among the 474 neonates with hyperbilirubinemia, 354 were diagnosed with ABO-HDFN (hemolytic group), while 120 were without ABO-HDFN (non-hemolytic group). The incidence of ABO-HDFN in neonates with blood type A (55.93%, 198/354) was significantly higher than those with blood type B (44.07%, 156/354) (P<0.05). Furthermore, neonates born to multiparous women had a significantly higher ABO-HDFN incidence (81.56%, 146/179) than first-born neonates (70.51%, 208/295) (P<0.05). Neonates in the hemolytic group had significantly lower hemoglobin levels (170.67±21.86 g/L vs 178.99±22.05 g/L, P<0.001), lower red blood cell counts (4.66±0.63×10 /L vs 4.89±0.59×10 /L, P<0.05), and lower hematocrit (50.05±6.56% vs 52.61±6.75%, P<0.05) compared to the non-hemolytic group. Additionally, the hemolytic group had significantly longer hospital stays (6 [5, 9] days vs 6 [4, 8] days), longer phototherapy duration (62 [38, 84.25] h vs 53 [34.25, 64.77] h), and higher frequency of jaundice episodes (9 [7, 13] times vs 8 [6, 12] times] compared to the non-hemolytic group (all P<0.05). Regression analysis indicated that a positive indirect Coombs test and multiparity were independent risk factors associated with prolonged phototherapy duration (P<0.05). Conclusion: ABO incompatibility is the leading cause of hemolytic disease in neonates, particularly in cases where the mother has blood type O and the neonate has blood type A. In such cases, close monitoring of bilirubin levels is strongly recommended. Multiparous pregnancies increase the risk of alloimmune hemolysis. Therefore, neonates born to multiparous women may require more frequent bilirubin monitoring and appropriate prenatal interventions when necessary. Additionally, changes in indicators such as hemoglobin level and red blood cell count should be closely monitored as early warning indicators for hemolytic anemia and bilirubin elevation.

This review article summarizes the current modification methods employed to enhance the osseointegration properties of polyetheretherketone (PEEK), a novel biomaterial. Our analysis highlights that strategies such as surface treatment, surface modification, and the incorporation of bioactive composites can markedly improve the bioactivity of PEEK surfaces, thus facilitating their effective integration with bone tissue. However, to ensure widespread application of PEEK in the medical field, particularly in oral implantology, additional experiments and long-term clinical evaluations are required. Looking ahead, future research should concentrate on developing innovative modification techniques and assessment methodologies to further optimize the performance of PEEK implant materials. The ultimate goal is to provide the clinical setting with even more reliable solutions.
Benzophenones ; Ketones/chemistry* ; Polyethylene Glycols/chemistry* ; Osseointegration ; Humans ; Polymers ; Biocompatible Materials/chemistry* ; Surface Properties ; Prostheses and Implants ; Dental Implants

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To observe the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in tumor tissue and peripheral blood CD8+T cells in patients with triple-negative breast cancer(TNBC),and to explore the ef-fect of tiragolumab on the function of CD8+T cells in the peripheral blood of these patients.Methods:The expression of TIGIT in tumor tissue of patients with TNBC was analyzed using The Cancer Genome Atlas(TCGA)database and immunohistochemical staining.Flow cytometry was employed to assess the co-expression of TIGIT and programmed death-1(PD-1)in peripheral blood CD8+T cells,as well as their cytokine secretion.A co-culture model of CD8+T cells and TNBC cell lines,HCC-1937 and MDA-MB-231,was estab-lished.The effect of tiragolumab on the anti-tumor activity of CD8+T cells in patients with TNBC was investigated using flow cytometry and confocal fluorescence imaging.Results:The expression of TIGIT in tumor tissue and peripheral blood CD8+T cells of patients with TNBC was significantly increased(P<0.05).Compared with the healthy control group,the TNBC group showed a significantly larger number of TIGIT+PD-1+CD8+T cells in the peripheral blood and significantly reduced secretion of interferon gamma(IFN-γ),tumor necrosis factor-α(TNF-α),and ginkgolide B(GB)by CD8+T cells;specifically,TIGIT+CD8+T cells demonstrated significantly re-duced secretion compared with TIGIT-CD8+T cells(P<0.05).Fol-lowing treatment with tiragolumab,TIGIT+CD8+T cells exhibited increased secretion of IFN-γ and TNF-α(P<0.05).In the co-culture model,tiragolumab restored the apoptosis-inducing ability of CD8+T cells in patients with TNBC,and this ability was further enhanced when it was combined with envafolimab.Conclusion:Ti-ragolumab restores the tumor-killing function of CD8+T cells by im-proving their immunosuppression.The combination of tiragolumab with envafolimab can further enhance its anti-tumor effect.

BACKGROUND:The stemness index may be associated with the prognosis and immune infiltration of sarcoma,but the specific regulatory mechanism and characteristic genes have yet to be fully elucidated. OBJECTIVE:To investigate the correlation between stem cells and prognosis as well as immune infiltration in sarcoma employing the gene stemness index model and to identify the ferroptosis signature genes associated with sarcoma stem cells. METHODS:The sarcoma RNA sequencing data and related clinical information were obtained from the Cancer Genome Atlas(TCGA).The sarcoma RNA sequencing data were grouped using the sarcoma stemness index.Survival data were used to analyze prognosis between groups.Differentially expressed genes were obtained for pathway enrichment and immune infiltration analysis.Ferroptosis-related differential genes were used to construct a protein interaction network and analyze prognostic correlation.Rhabdomyosarcoma cell lines were cultured and divided into adherent cell group and stem cell group.The adherent cell group received no intervention,while the stem cell group was treated with serum-free culture to enrich stem cells in rhabdomyosarcoma cells.qRT-PCR was used to evaluate stemness markers,ferroptosis-related genes,and mRNA expression of ferroptosis-related markers in the cells. RESULTS AND CONCLUSION:(1)Patients were divided into high and low stemness index groups based on the median stemness index.The progression-free survival of patients in the high stemness index group was lower than that in the low stemness index group by disease risk prediction,suggesting poor prognosis.(2)According to GO and KEGG analysis,the groups with high and low stemness indices differed from one another.There were differences in immune infiltration between the high and low stemness index groups.Nine of the 23 ferroptosis-related genes in the differential genes have the potential to establish a highly correlated network of protein interactions.Patients with high expression of IDO1,IFNG,and AQP5 have a better prognosis,while those with high expression of CA9 have a poor prognosis.(3)The qRT-PCR results demonstrated a significant upregulation of stem cell-related markers NANOG,SOX2,and OCT4 mRNA expressions in the stem cell group compared to the adherent cell group(P<0.05).Compared to the adherent cell group,the stem cell group exhibited decreased mRNA expression level of ferroptosis-related marker SLC7A11(P<0.05)while showing increased levels of ACSL4,GPX4,FTH1,and COX2(P<0.05).Compared to the adherent cell group,the stem cell group displayed decreased mRNA expression level of differentially expressed gene CA9 alongside elevated levels of IDO1,IFNG,and AQP5(P<0.05).Stem cells were strongly associated with sarcoma survival and ferroptosis by bioinformatics analysis and experimental verification.Sarcoma stem cells have aberrant expression of CA9,IDO1,IFNG,and AQP5,which may serve as new targets for sarcoma therapy as well as diagnostic indicators.