BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.

Parkinson’s disease （PD） is a common chronic neurodegenerative disease with movement disorders as the main clinical manifestation. The nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway is closely associated with the occurrence and progression of PD. TCM flavonoid monomers （luteolin， rutin， etc.）， alkaloids （camptothecin， sinomenine， and alkaloids extracted from Uncaria rhynchophylla）， terpenes （tanshinone ⅡA， carvacrol， paeoniflorin）， phenols （ellagic acid， rosmarinic acid）， saponins （ginsenoside RK1）， and traditional Chinese medicine compounds （Wuzi yanzong pill and PD formula-2） can resist oxidative stress damage， inhibit inflammatory responses and abnormal aggregation of α-synuclein， and regulate neurotrophic factors by activating the Nrf2/HO-1 signaling pathway， thereby alleviating dopaminergic neuronal damage.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

Objective: To identify the phenotypes, antibodies and explore the molecular mechanisms of a patient who carries antibodies to RBC high-frequency antigens and his family members. Methods: The antibody identification test was performed for the proband by serological methods, and targeted NGS was subsequently used to detect mutations that occurred in blood group genes. Blood samples were collected from the proband and his family members. Sanger sequencing was used to verify the mutation of the XK gene. The expression of Kell blood group antigens was detected by serological methods and flow cytometry. K cells were used to detect the antibody specificity of the proband. The morphology of red blood cells was detected by the scanning electron microscopy. The serum creatine kinase levels of the proband and his family members were analyzed by colorimetric methods. Results: The results of the antibody identification test suggested that the proband might have antibodies to high-frequency antigens. NGS results suggested a homozygous mutation (c. 107G>A) in exon 1 of the XK gene in the proband, resulting in a truncated XK protein. The Sanger sequencing results of the proband were consistent with the NGS results, and the mutation was not found in other family members. The expression of Kell blood group antigens of the proband was not found by serological methods and flow cytometry. The results of the antibody specificity test showed that the proband had anti-Km antibodies. Spike-like changes were identified on red blood cells, and serum creatine kinase level was elevated in the proband. Conclusion: In this study, the McLeod phenotype caused by homozygous mutation (c. 107G>A) of XK gene was identified in Chinese individuals for the first time by the phenotype and molecular mechanism studies. The results of genotyping and phenotyping suggested that the McLeod phenotype caused by the mutation was compatible with the phenotypes of McLeod and K .

Objective:To explore the assessment value of liver enzyme changes before and after hepatectomy on the prognosis of patients with primary hepatocellular carcinoma(HCC). Methods:A retrospective analysis was conducted on the clinical data of 421 patients with primary HCC who received at the First and Second Affiliated Hospitals of Xi'an Jiaotong University from January 2016 to December 2020.The univariate and multivariate COX regression analyses were used to screen the risk factors affecting the prognosis of patients with primary HCC,and the optimal cut-off value was selected to group the most valuable indicators among them,further analyzing the different factors among subgroups.The Kaplan-Meier method was used to assess the prognosis of the subgroups,and the survival curves were plotted and statistically tested. Results:Multivariate COX regression analysis revealed that Barcelona Clinic Liver Cancer(BCLC)stage,tumor number,alpha-fetoprotein(AFP),the quantitative change of γ-glutamyl transpeptidase(GGT)and total bilirubin(TBIL)before and after surgery were independent risk factors affecting the prognosis of patients with primary HCC(P＜0.01),and there were differences in hepatitis B virus surface antigen(HBsAg),TNM stage,BCLC stage,tumor size,tumor number,tumor differentiation degree,AFP,surgery type,intraoperative bleeding volume,postoperative albumin-bilirubin(ALBI)and white blood cell count between the high and low GGT variation groups(P＜0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with primary HCC between the high and low GGT variation groups was significantly different,with a hazard ratio of 2.603 for mortality and 1.449 for recurrence(both P＜0.01). Conclusion:The quantitative change of GGT before and after hepatectomy has an evaluation value for the prognosis of patients with primary HCC,and the quantitative change of GGT greater than 29.5 is an independent risk factor for the prognosis of patients with primary HCC.

Objective To explore the efficacy of repetitive peripheral magnetic stimulation(rPMS)in patients with lumbar disc herniation(LDH).Methods From March 2023 to March 2024,60 LDH patients were recruited in the inpatient or outpatient department of the rehabilitation department of a tertiary hospital.All patients were randomly assigned to the rPMS group or the conventional group,30 cases in each group.Both groups received routine physical therapy,and the rPMS group was treated with rPMS on this basis.VAS,JOA,and neurophysiological tests were performed before intervention and 2 weeks after intervention.Results The VAS and JOA scores of the two groups were significantly lower than those before treatment(P<0.05).Compared with the conventional group,the VAS and JOA scores of the rPMS group were significantly lower(P<0.05).Compared before and after treat-ment,the neuroelectrophysiological examination of the rPMS group was significantly improved(P<0.05).After 2 weeks of treatment,the tibial nerve motor conduction velocity,H reflex latency and IP peak in the conventional group were significantly faster than those before treatment(P<0.05).After 2 weeks of treatment,compared with the conventional group,there were significant differences in tibial nerve motor conduction velocity,peroneal nerve motor conduction velocity,superficial peroneal nerve sensory conduction velocity,sural nerve sensory conduction velocity,H reflex latency and IP peak(P<0.05).Conclusion rPMS can significantly improve and restore pain and nerve injury in patients with LDH.rPMS can be used as an effective adjuvant therapy.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

Purpose To investigate the relationship be-tween the level of tumor abnormal protein(TAP)and the molec-ular subtypes and clinicopathological features of breast cancer,and to analyze the value of TAP in breast cancer screening,di-agnosis and prognosis prediction.Methods The clinical data of 357 breast cancer patients were collected,and the elbow venous blood was collected to detect the TAP condensate area.Immuno-histochemical(IHC)EnVision two-step method was used to de-tect the expression of AR,ER,PR,HER2,p53 and Ki67,and FISH to detect HER2 gene.The relationship between TAP ex-pression and clinicopathological features,molecular subtypes and clinical stages of breast cancer was analyzed,and the rele-vant literature was reviewed.Results Among 357 breast cancer patients,9 cases(2.52％)were TAP negative,36 cases(10.08％)were weakly positive,312 cases(87.40％)were strongly positive,and the positive rate of TAP was 97.48％.AR was positive in 321 cases and negative in 36 cases,ER was pos-itive in 256 cases and negative in 101 cases,PR was positive in 214 cases and negative in 143 cases,HER2 was strongly posi-tive in 98 cases,weakly positive in 214 cases and negative in 45 cases,p53 was positive in 146 cases and negative in 211 cases,Ki67 index was ≥20％in 276 cases and＜20％in 81 case.A total of 155 cases of IHC HER2(2+)breast cancer were tested by FISH:140 cases were negative and 15 cases were positive.The expression level of TAP in patients of ≥50 years old expres-sionas significantly higher than that in patients of＜50 years old(P＜0.05).The expression level of TAP in patients with high Ki67 proliferation index was significantly higher than that in pa-tients with low Ki67 proliferation index(P＜0.05).There was a significant difference in TAP expression between patients with different molecular subtypes(P＜0.05).Tap expression was higher in triple-negative breast cancer patients than in non-tri-ple-negative breast cancer patients(P＜0.05),and it was high-er in Luminal B breast cancer patients than in non-Luminal B breast cancer patients(P＜0.05).There was a significant difference in TAP expression between patients with different clin-ical stages(P＜0.05),and TAP expression level was positively correlated with clinical stage in breast cancer.Conclusion TAP detection can improve the diagnostic accuracy of breast cancer,and has a certain correlation with the survival rate and prognosis of breast cancer patients.

Objective To investigate the associations of the single nucleotide polymorphism (SNP) rs2304733 in TEA domain transcription factor 1 (TEAD1) , rs7135838 and rs1990330 in TEA domain transcription factor 4 (TEAD4) genes with the risk of non-cardia gastric carcinogenesis.Methods Enzyme linked immunosorbent assay (ELISA) was used to detect specific antibodies against Helicobacter pylori(Hp) in serum samples of the normal con-trol group.470 normal controls were divided into Hp infection negative group (n=223) and positive group (n=247) based on antibody titers.In the 450 non-cardia gastric cancer cases and 470 controls, polymerase chain reac-tion-restriction fragment length polymorphism (PCR-RFLP) was used to genotype the each SNP locus.The uncon-ditional Logistic regression method was used to evaluate the associations between each SNP locus and the risk of non-cardia gastric carcinogenesis.Results The SNPs of TEAD1 and TEAD4 were not associated with Hp infec-tion.TEAD1 rs2304733 was associated with the risk of non-cardia gastric cancer.Compared with the carriers of TT genotype, the carries of CT and CC genotypes had an increased risk of non-cardia gastric cancer (CT vs TT:OR=2.321 , 95％CI:1.690-3.188;CC vs TT:OR=5.140 , 95％CI:1.080-24.463) .TEAD4 rs1990330 was as-sociated with the risk of non-cardia gastric cancer.Compared with the carriers of GG genotype, those with GT geno-type had an increased risk of non-cardia gastric cancer (OR = 2.405 , 95％ CI: 1.480 - 3.908) .TEAD4 rs7135838 was not associated with the risk of non-cardia gastric cancer.TEAD1 rs2304733, TEAD4 rs7135838 and rs1990330 had interaction effects on the risk of non-cardia gastric cancer (P<0.05).Conclusion In Baotou Han population, TEAD1 rs2304733 and TEAD4 rs1990330 do not play a major role in Hp infection, but may play a role in the risk of non-cardia gastric cancer.TEAD4 rs7135838 may not play a major role in the risk of Hp infec-tion and non-cardia gastric cancer.TEAD1 rs2304733 and TEAD4 rs1990330 have the strongest synergistic effect on the risk of non-cardia gastric cancer, which is the best interaction model.

Objective:To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes.Methods:There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People′s Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes.Results:There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages ( P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics ( P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA ( P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups ( P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types ( P<0.05). Conclusions:Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients′ age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.