Objective: To explore the feasibility, precision, and clinical value of a personalized primary repair approach centered on digital design, integrating 3D printing technology with multiple materials such as titanium mesh, polyetheretherketone (PEEK), and titanium plates, for complex craniofacial bone defects involving the skull, mandible, orbit, and zygoma resulting from traffic accidents, providing a reference for primary repair of clinically complex craniofacial bone defects. Methods: One patient who was admitted in September 2021 with multiple comminuted fractures of the right craniomaxillofacial region and large-area bone defects caused by a traffic accident was selected. Digital design was integrated throughout the entire repair process. First, preoperative computed tomography (CT) data were used for 3D reconstruction of the craniomaxillofacial region; then, based on the model, the anatomical contour of the healthy left side was reproduced via mirroring technology for the defects on the right side. A targeted repair plan was designed: 3D-printed PEEK material was used to reconstruct the right orbital floor and zygomaticomaxillary complex, a 0.6-mm-thick titanium mesh was adopted to repair the right skull defect, and a 2.0-mm-thick titanium plate was applied for rigid internal fixation of the mandibular fracture. A one-stage repair surgery was completed simultaneously. In addition, a literature review was conducted on studies related to the repair of complex combined craniomaxillofacial defects. Results: CT examination at 1 week postoperatively showed that the average fitting gap of the implants was 0.3 mm, and the symmetry difference of the facial contour was less than 5 mm. At 3 months postoperatively, the patient’s maximum mouth opening reached 38 mm, the occlusal relationship returned to normal, and the diplopia symptom completely disappeared. During the 6-month postoperative follow-up, no complications such as implant loosening, infection, or displacement occurred; the FACE-Q scale score was 91, indicating a high level of subjective patient satisfaction. The literature review indicated that digital design combined with 3D printing technology can significantly improve the accuracy of complex craniomaxillofacial bone defect reconstruction. PEEK material is suitable for the reconstruction of the orbital floor and zygomaticomaxillary complex. Titanium mesh and plates can ensure the stability of the reconstruction. Multi-materials combined reconstruction represents an important therapeutic strategy for such defects. Conclusion The individualized one-stage repair scheme, centered on digital design and combined with 3D printing technology and multi-materials (titanium mesh, PEEK, and titanium plates), can achieve precise anatomical reduction and simultaneous functional recovery for complex combined craniomaxillofacial bone defects caused by traffic accidents.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective To investigate the clinical effect and safety of bronchial arterial chemoembolization(BACE)combined with micro wave ablation(MW A)and immunotherapy in treating patients with advanced lung squamous cell carcinoma.Methods The clinical data of 68 patients with advanced lung squamous cell carcinoma,who were admitted to the North Jiangsu People's Hospital of China from June 2020 to June 2022 to receive treatment,were retrospectively analyzed.According to the therapeutic method,the patients were divided into control group(n=30,receiving BACE combined with immunotherapy)and observation group(n=38,receiving BACE followed by MW A,which was performed with CT-guided localization of the lung lesion,and immunotherapy in 3-5 days after BACE).Results The surgical success rate in both the 30 patients of the observation group and the 38 patients of the control group was 100％.After treatment,no surgery-related or chemoembolization-related serious complications occurred in both groups.In the control group and the observation group,the mean progression-free survival(PFS)was(5.70±1.61)months and(12.10±0.72)months respectively,the mean overall survival(OS)was(11.80±1.10)months and(13.00±1.13)months respectively.The PFS of the observation group was obviously longer than that of the control group(P＜0.05),and no statistically significant difference in OS existed between the two groups(P=0.255).Conclusion BACE combined with MW A and immunotherapy can effectively control the advanced lung squamous cell carcinoma,it has reliable short-term efficacy when compared with BACE plus immunotherapy,and it can inhibit tumor growth and prolong the PFS of patients,with a trend of extending OS and a satisfactory clinical safety.

Objective To investigate the safety and efficacy of super-selective arterial embolization in the treatment of abdominal wall hematoma.Methods The clinical data of 11 patients with abdominal wall hematoma,who were admitted to the Northern Jiangsu People's Hospital of China from January 2018 to December 2023,were retrospectively analyzed.All patients received angiography together with super-selective arterial embolization.The effectiveness of embolization treatment was evaluated by the technical success rate and therapeutic effect,and the safety was evaluated by the incidence of complication.Results The median age of the 11 patients was 70 years,91％were female,with a body mass index(BMI)of 25.1 kg/m2,subcutaneous fat thickness of 2.8 cm,and international normalized ratio(INR)of 1.12.DSA showed that 8 patients(72％)had active bleeding signs,3 patients(28％)had no active bleeding signs.Under DSA,a total of 18 responsible vessels,including 6 lumbar arteries(33.3％),5 deep circumflex iliac arteries(27.7％),5 inferior epigastric arteries(27.7％)and 2 iliolumbar arteries(11.3％),were identified and were treated with embolization.The median time spent for operation was 80 minutes.The technical success rate was 100％and the clinical effective rate was 91％.No operation-related major complications occurred,and the median hospital stay was 6 days.Conclusion For the abdominal wall hematoma in aged,obesity patients with underlying diseases,super-selective arterial embolization is a therapeutic method with high technical success rate,high clinical effective rate and satisfactory clinical safety.

Objective To discuss the clinical efficacy of microwave ablation(MWA)combined with percutaneous vertebroplasty(PVP),radiofrequency ablation(RFA)combined with PVP,and simple PVP in the treatment of vertebral metastatic tumors.Methods A total of 65 patients with vertebral metastatic tumors,who were admitted to the Northern Jiangsu People's Hospital of China to receive treatment from January 2019 to June 2023,were enrolled in this study.The patients were divided into MWA plus PVP group(M+P group,n=25,27 diseased vertebral bodies in total),RFA plus PVP group(R+P group,n=20,23 diseased vertebral bodies in total),and simple PVP group(P group,n=20,24 diseased vertebral bodies in total).Visual analog scale(VAS)score was used to assess the preoperative pain degree and the postoperative relief degree.Bone cement distribution and leakage at one week after surgery were evaluated.Results Successful operation was accomplished in all of the patients.No serious procedure-related complications occurred in all the patients of three groups.In R+P group,P group and M+P group,the preoperative mean VAS scores were(8.48±0.80)points,(8.57±0.98)points and(8.20±1.00)points respectively;the differences among the three groups were not statistically significant(P＞0.05).One week after operation,the pain was significantly relieved in all the patients of three groups;the mean VAS scores in R+P group,P group and M+P group were(4.10±0.85)points,(3.17±0.93)points and(2.44±1.23)points respectively,and the reduction in VAS score was most pronounced in M+P group(P＜0.05).Six months after operation;the mean VAS scores in R+P group,P group and M+P group were(1.87±0.84)points,(4.60±1.09)points and(1.48±0.71)points respectively;and the reduction in VAS score was most pronounced in the M+P group(P＜0.05).The used amount of bone cement in M+P group,R+P group and P group was(7.54±1.44)mL,(5.48±1.12)mL and(4.59±1.56)mL respectively,the difference among the three groups was statistically significant(P＜0.05).The vascular leakage rate(34.8％)and non-vascular leakage rate(52.2％)in P group were remarkably higher than those in R+P group and in M+P group(P＜0.05).No statistically significant difference in the rate of cement leakage existed between R+P group and M+P group(P＞0.05).Conclusion For the treatment of vertebral metastases,MW A plus PVP is superior to RFA plus PVP in pain relief rate.

Objective: To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis. Methods: Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay. Results: The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) . Conclusion The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Objective: This study aimed to compare outcomes and adverse events of patients with locally advanced cervical cancer (LACC) undergoing concurrent chemoradiotherapy (CCRT) with cisplatin single-agent chemotherapy vs. CCRT with cisplatin combined with paclitaxel dualagent therapy. The primary outcomes are overall survival (OS), progression-free survival (PFS), local recurrence (LR), distant metastasis (DM) and the occurrence of adverse events. Methods: This retrospective cohort study included patients with FIGO 2009 stage IB1-IVA cervical squamous cell carcinoma undergoing radical CCRT. Patients were divided into groups A and B, treatment outcomes were compared between the two groups after 1:1 proportional propensity score matching. Results: Medical records of 1,203 patients were reviewed and 572 patients were finally included for propensity score matching. After propensity score matching, 121 pairs of patients were selected for analysis. The OS, PFS, LR and DM rates were 78.5% and 83.5% (p=0.417), 73.3% and 78.5% (p=0.312), 6.6% and 2.5% (p=0.123), 19% and 15.7% (p=0.497) for groups A and B, respectively. Further subgroup analysis according to stage and lymph node metastatic status showed no difference in survival between the two groups. The incidence of grade 3–4 acute haematological toxicities was different between the two groups (p<0.05). Conclusion Cisplatin combined with paclitaxel CCRT couldn’t improve the survival rates of patients with LACC. However, the hematological toxicity of combination chemotherapy is more severe but controllable. Cisplatin single-agent therapy remains the first choice for CCRT. Further prospective studies are indicated to provide evidence for the efficacy of cisplatin plus paclitaxel in dual-agent concurrent therapy.

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.