Objective Logistic regression model was used to analyze the risk factors of liver cancer in patients with hepatitis B virus-related cirrhosis. Methods A retrospective analysis was performed on 504 patients with hepatitis B cirrhosis who were treated in a hospital from April 2021 to April 2024. The occurrence of liver cancer was counted. The risk factors of liver cancer in patients with HBV-related cirrhosis were analyzed by logistic regression analysis. Results Among the 504 patients with hepatitis B cirrhosis, 101 patients developed liver cancer and 403 patients did not develop liver cancer, which were included in the liver cancer group (n=101) and the non-liver cancer group (n=403).. Among hepatitis B cirrhosis, the incidence rate of liver cancer was 20.04%. Compared with the non-liver cancer group, the proportion of patients with long-term drinking history, family history of liver cancer, history of diabetes mellitus, antiviral therapy, and HBV-DNA load>104 were higher in the liver cancer group (P<0.05). logistic regression analysis found that long-term drinking history (OR=3.077, 95%CI: 1.130-8.378, P=0.028), history of diabetes mellitus (OR=3.747, 95%CI: 1.765-7.954, P=0.001), no antiviral therapy (OR=3.466, 95%CI: 1.337-8.985, P=0.011) and HBV-DNA load>104 (OR=3.149, 95%CI: 1.353-7.328, P=0.008) could independently affect the occurrence of liver cancer in patients with hepatitis B cirrhosis. Conclusion According to logistic regression analysis, long-term drinking history, history of diabetes mellitus, no antiviral therapy, and HBV-DNA load>104 are risk factors for liver cancer in patients with HBV-related cirrhosis.

OBJECTIVE: To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications. METHODS: By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes. RESULTS: The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway. CONCLUSION LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans ; Mouth Neoplasms/metabolism* ; Prognosis ; Carcinoma, Squamous Cell/metabolism* ; Biomarkers, Tumor/metabolism* ; LIM Domain Proteins/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Male ; Female

OBJECTIVE: To evaluate the clinical outcomes and define the indications for a one-stage mandibular reconstruction technique that combines iliac bone flaps with immediate implant-based dentures, and to assess both the accuracy of surgical planning and the long-term success of the procedure. METHODS: A total of ten patients underwent the procedure at Peking University Hospital of Stomatology between June 2020 and August 2023. The preoperative biopsy pathology of all the patients confirmed a benign tumor. In this technique, iliac bone flaps were used for mandibular reconstruction, and immediate implant-based dentures were placed during the same surgical session. Various outcome measures were evaluated, including the accuracy of the surgical reconstruction, implant placement deviations (entry point, apical point, depth, and angle), and long-term outcomes, such as cervical bone resorption, implant survival, and the cumulative survival rate. RESULTS: Thirty-eight implants were successfully inserted into the iliac flaps of the ten patients. The median follow-up duration was 23.5 months, and no significant complications occurred during the follow-up period, such as infections, titanium plate exposure, implant loosening, or damage to the implants and dentures. The accuracy of preoperative virtual surgical planning (VSP) was highly reliable. The repeatability of the VSP model compared to the postoperative reconstructed mandible was as follows: 67.82% ±10.16% within 1 mm, 82.14% ±6.58% within 2 mm, and 90.61% ±4.62% within 3 mm. The average maximum deviation from the plan was (6.10±0.89) mm, with an average overall deviation of (1.14±0.31) mm. For the implants, deviations in critical parameters were as follows: entry point deviation was (2.02±0.58) mm, apical point deviation was (2.25± 0.66) mm, depth deviation was (1.26±0.51) mm, and angular deviation was 1.84°±1.10°. The implant survival rate remained 100% during the follow-up, with a cumulative survival rate of 97.37% from 1 to 4 years. Average cervical bone resorption was 0.94 mm. CONCLUSION The combination of iliac bone flaps with immediate implant-based dentures for one-stage mandibular reconstruction demonstrated pro-mising clinical outcomes, including high implant survival and minimal complications. This technique proved to be safe and reliable for mandibular reconstruction. However, further studies with larger sample sizes and longer follow-up periods are necessary to confirm the long-term efficacy and optimal indications for this procedure.
Humans ; Mandibular Reconstruction/methods* ; Male ; Ilium/surgery* ; Female ; Middle Aged ; Surgical Flaps ; Adult ; Mandible/surgery* ; Aged ; Dental Implantation, Endosseous/methods* ; Immediate Dental Implant Loading/methods* ; Bone Transplantation/methods* ; Dental Implants

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced cell lysis and necrosis lead to the passive release of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) into circulation. These DNAs bind to pattern recognition receptor (PRR), triggering excessive inflammatory cytokines production and increasing mortality. Three prime repair exonuclease 1 (TREX1) is a 3' to 5' exonuclease that rapidly degrades single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) by cleaving phosphodiester bonds. This process can prevent the accumulation of damaged DNA in the cytoplasm, thereby averting abnormal inflammation and pathological immune responses. TREX1 thus plays a significant role in regulating DNA-related damage caused by sepsis. However, the role and underlying mechanisms of TREX1 in sepsis have not been thoroughly discussed. This review aims to elucidate the structure and function of TREX1 and its mediated immune regulatory mechanisms, with the hope of clarifying the potential role of TREX1 in the field of sepsis.

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

AIM: To explore the predictive value of the combination of triglyceride-glucose(TyG)index, nesfatin-1, and retinol-binding protein 4(RBP4)for diabetic retinopathy, and provide evidence for early prediction of DR.METHODS: The clinical data of 164 patients with type 2 diabetes mellitus(T2DM)who admitted to the hospital between February 2022 and December 2023 were retrospectively collected. Based on the fundus examination results, these patients were divided into two groups: the DR group(n=43), including proliferative DR(PDR, n=19)and non-proliferative DR(NPDR, n=24), and the T2DM without DR group(n=121). The TyG index and the level of nesfatin-1 and RBP4 were measured after admission.RESULTS:T2DM patients with DR had a longer disease duration compared with T2DM patients without DR, and the DR group had higher fasting blood glucose, glycosylated hemoglobin, triglyceride, total cholesterol, low-density lipoprotein, TyG index, and RBP4 levels, while lower high-density lipoprotein and nesfatin-1 levels(all P<0.001). Multivariate Logistic regression analysis indicated that the duration of T2DM(OR=1.338, 95%CI: 1.059-1.690), glycosylated hemoglobin(OR=5.065, 95%CI: 1.659-15.470), low density lipoprotein(OR=12.715, 95%CI: 2.385-67.790), TyG index(OR=23.057, 95%CI: 2.936-181.073)and RBP4(OR=1.319, 95%CI: 1.028-1.692)were the independent risk factors for DR, while nesfatin-1(OR=0.007, 95%CI: 0.003-0.016)was an independent protective factor for DR. The ROC curves were drawn, and the results indicated that the TyG index, nesfatin-1, and RBP4 had certain predictive values for DR patients with T2DM, with areas under curve(AUC)of 0.804, 0.878 and 0.738, respectively. The combined AUC of the TyG index, nesfatin-1, and RBP4 was 0.946, sensitivity was 83.72%, and specificity was 92.56%. Patients with PDR had a higher TyG index, higher RBP4 level, and lower nesfatin-1 level than patients with NPDR(all P<0.05). Spearman's correlations indicated a positive association between the TyG index, RBP4 and DR degree, and a negative association between nesfatin-1 and DR degree(rs=0.557, 0.392, -0.359, repectively, all P<0.05). Pearson correlation analysis indicated a negative correlation between the TyG index and the levels of nesfatin-1, a positive correlation between the TyG index and the levels of RBP4, and a negative correlation between the levels of nesfatin-1 and RBP4 in DR patients with T2DM(r=-0.486, 0.538, -0.592, all P<0.05).CONCLUSION: The serum of TyG index and the levels of nesfatin-1 and RBP4 were early predictive markers for DR and were associated with the risk of the occurrence and severity of the disease. Besides, the combined prediction performance of TyG index, nesfatin-1, and RBP4 was better for DR.

Background Mercury, as a global heavy metal pollutant, poses a serious threat to human health. The toxicity of mercury depends on its chemical form. Distinguishing the forms of mercury in the environment is of great significance for mercury management and reducing human mercury exposure risks. Objective To establish a non-targeted metallomics method based on synchrotron radiation X-ray fluorescence (SRXRF) spectroscopy combined with machine learning to screen inorganic mercury (IHg) or methylmercury (MeHg) exposed rice plants. Methods Rice seeds were exposed to ultra-pure water (control group), 0.1 mg·L⁻¹ IHg (IHg group) or MeHg (MeHg group) solutions, respectively. After germination, the seedlings were cultured for 21 d, and rice leaves were collected, dried, weighed, and pressed. The content of metallome in rice leaves was determined by SRXRF. Machine learning models including soft independent modeling cluster analysis (SIMCA), partial least squares discriminant analysis (PLS-DA), and logistic regression (LR) were used to classify the SRXRF full spectra of different groups and find the best model to distinguish rice exposed to IHg or MeHg. Besides, characteristic elements were selected as input parameters to optimize the model by improving computing speed and reducing model calculation. Results The SRXRF spectral intensities of the control group, IHg group, and MeHg group were different, indicating that exposure to IHg and MeHg can interfere the homeostasis of metallome in rice leaves. The results of principal component analysis (PCA) of SRXRF spectra showed that the control group could be well distinguished from the mercury exposed groups, but the IHg group and the MeHg group were mostly overlapped. The accuracy rates of the three models (PLS-DA, SIMCA, and LR) were higher than 98% for the training set, higher than 95% for the validation set, and higher than 94% for the cross-validation set. Besides, the accuracy of the LR model was higher than that of the PLS-DA model and the SIMCA model. Furthermore, the accuracy was 92.05% when using characteristic elements K, Ca, Mn, Fe, and Zn selected by LR to distinguish the IHg group and the MeHg group. Compared with the full spectra model, although the prediction accuracy of the characteristic spectral model decreased, the input parameters of the model decreased by 99.51%, and precision, recall, and F1 score were above 84.48%, indicating that the model could distinguish rice exposed to different mercury forms. Conclusion Non-targeted metallomics method based on SRXRF and machine learning can be applied for high-throughput screening of rice exposed to different forms of mercury and thus decrease the risks of people being exposed to mercury.