BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

BACKGROUND:The number of patients receiving total knee arthroplasty has been increasing globally each year.Pain management is a crucial aspect following total knee arthroplasty,as effective pain control can facilitate early mobilization,reduce complications,enhance patient satisfaction,and accelerate the rehabilitation process.OBJECTIVE:To construct a visual map of post-total knee arthroplasty pain,understand the international research status and trends in this field,and provide a reference for future studies.METHODS:Relevant research articles on post-total knee arthroplasty pain were retrieved from the CNKI,WanFang Data,and Web of Science core databases,covering the period from January 2000 to December 2023.The CiteSpace software(version 6.2.3)was used to analyze the annual publication output,authors,institutions,countries,keywords,and references.Utilizing R programming language(version 4.4.1),a database was established to create line charts and bar graphs.RESULTS AND CONCLUSION:(1)Our analysis included 3 796 publications,predominantly in Chinese(3 509 articles)with the remainder in English(287 articles).(2)The United States was the most productive country in English literature,with Harvard University leading institutional output.Guangzhou University of Chinese Medicine was the top publishing institution in Chinese literature.(3)Keyword clustering identified"quality of life,""phobia,"and"acupuncture"as emerging focal points in Chinese literature,while"satisfaction"and"psychological factors"were prominent in English literature over the past five years.Co-occurrence and clustering analysis revealed dense internal connections among institutions,authors,and publications,but sparse external collaborations.(4)The study's bias on visualization analysis may have introduced bias by excluding less influential papers.(5)Regarding research hotspots,domestic research emphasized the efficacy and exploration of analgesic methods,in contrast to international research that focused on pain mechanism subtyping and analgesic drug innovation.Future research is expected to trend towards traditional Chinese medicine for postoperative pain,multimodal analgesia,and the investigation and prevention of pain typing mechanisms.

Ferroptosis exhibits a clear “double-edged sword” effect in liver fibrosis， with its impact strictly dependent on the type of target cells. In hepatocytes， ferroptosis induced by specific signaling pathways （such as glutathione peroxidase 4 inhibition） is a key factor for driving hepatic injury and initiating fibrogenesis， and dying hepatocytes activate hepatic stellate cells by releasing damage-associated molecules； on the contrary， in activated hepatic stellate cells， ferroptosis becomes a therapeutic target for promoting liver fibrosis regression， and selective elimination can be achieved by disrupting their distinctive antioxidant defense mechanisms. Moreover， ferroptosis modulates the dynamic balance of the fibrotic liver microenvironment by regulating macrophage polarization and intercellular communication. Based on the above mechanisms， targeting ferroptosis has emerged as a promising strategy for precise treatment. This article summarizes related research advances and discusses the major challenges and future directions for clinical translation.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To constructCSF1R+/-mice and to analyze their genotypes, so as to provide animal model basis for disease pathological mechanism and drug target. Methods : A linearized targeting vector was designed according to Cre/Loxp system. A Loxp site was inserted upstream of the 5th exon of theCSF1Rgene, and a neomycin resistance box with Loxp sites on both sides was inserted downstream of the 5th exon. The linearized targeting vector was electroporated into embryonic stem cells. The correctly targeted embryonic stem cells were injected into the blastocysts of C57BL/6J mice to obtain chimeric mice, which were bred with Zp3-Cre mice. The newborn mice were numbered 9-14 days after birth and their tails were cut. The DNA of the mice was extracted, and the genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. The expression of CSF1R in mouse macrophages was detected by flow cytometry. The expression of CSF1R in mouse tissues was detected by Western blot. Results: The results of agarose gel electrophoresis showed that 453 bp bands were amplified in wild type mice, and 453 bp and 650 bp bands were amplified in heterozygous mice. The results of flow cytometry showed that the expression of CSF1R in peritoneal macrophages and bone marrow-derived macrophages of CSF1R heterozygous mice was lower than that of WT group(P<0.05). The results of Western blot showed that the expression of CSF1R in spleen, kidney and brain tissue of CSF1R heterozygous group was lower than that of WT group(P<0.05). Conclusion CSF1R+/-mice are successfully constructed, reproduced and identified, which provides an animal model basis for further revealing the potential mechanism of CSF1R in immune regulation.

Objective The data related to adverse drug reaction of trastuzumab deruxtecan(T-DXd)were mined to provide references for its clinical management and adverse event handling.Methods Based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data reported from the post-marketing period of T-DXd until the fourth quarter of 2024 were extracted.The proportion imbalance method,specifically the reporting odds ratio(ROR)method,was used to mine and analyze the data related to adverse events of T-DXd.Results A total of 13 134 cases of adverse events related to T-DXd were obtained from the FAERS database.Gastrointestinal disorders were the most common,with 2348 adverse reaction signals,accounting for 17.88％.The most frequent adverse reactions were nausea(n=809),interstitial lung disease(n=732),and fatigue(n=579).The one with the highest ROR value was Listeriosis gastroenteritis(ROR=1228.74).The highest number of deaths were from interstitial lung disease(226),pneumonitis(90),and nausea(67).Conclusion By mining data on real-world adverse drug reaction related to T-DXd,suggests that pulmonary function,cardiac function,complete blood count and other parameters should be closely monitored during treatment for early diagnosis and treatment of corresponding complications.

Objective:To establish a new method and platform for screening, identifying, and exploring a new strategy for anti-hepatitis B immunotherapy based on hepatitis B virus (HBV)-specific TCR.Methods:Peripheral blood mononuclear cells were isolated from patients with acute hepatitis B. CD3 +CD8 +CD137 +T single cells were sorted out after stimulation with the HBsAg peptide library. The α and β chains in TCRs of single cells were amplified by PCR. TCR double-chain pairing and lentiviral packaging were performed through high-throughput sequencing. Re-infected Jurkat-76-NFAT-GFP cells and the cell lines stably expressing TCR were screened. HBsAg peptide library and immortalized B lymphocytes co-cultured with J76N-TCR were used to screen HBsAg-specific TCRs. K562 cell lines stably expressing HLA-A*24:02 were established to determine epitope peptide by screening A*24:02-restricted TCR. The screened TCRs were replaced with mouse C regions and packaged with lentiviruses. Functional validation was performed on healthy human CD4 +T and CD8 +T lymphocytes following infection. Results:Stable TCR-expressing cell lines were successfully prepared based on single-cell TCRαβ double-chain amplification and pairing technology. Twenty-one TCRs were screened using immortalized B lymphocytes, resulting in nine possible HLA-A*24:02-restricted HBsAg-specific TCRs. Further screening with K562-A2402 resulted in six A*24:02-restricted HBsAg-specific TCRs with identically recognized epitope peptide. The functional determination of the two TCR clones revealed their specific recognition function for target cells expressing HBsAg.Conclusion:HLA-A*24:02-restricted HBsAg-specific TCR with recognition function for target cells expressing HBsAg was successfully obtained based on the new experimental technology system, laying an important foundation for further exploration of antiviral immunotherapy based on HBV-specific TCR.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Objective To explore the value of MR T2WI-spectral attenuated inversion recovery(T2WI-SPAIR)sequence and dif-fusion tensor imaging(DTI)in the recovery process of vertebral compression fractures over time.Methods Three patients aged 60-75 years with a clear time and mechanism of injury were selected.They underwent conventional MR sequences and DTI scans at eight time points.The morphological and signal changes of the fractured vertebrae on T2WI-SPAIR sequences were dynamically observed.Statistical analysis was performed on the apparent diffusion coefficient(ADC)and fractional anisotropy(FA)of the fractured verte-brae and adjacent normal vertebrae.Results T2WI-SPAIR sequence showed that the vertebral morphology gradually worsened from the initial mild compression changes over time after vertebral fracture.Local bone collapse occurred at the upper edge of the verte-brae at>7-9 weeks,followed by stabilization.The initially diffuse and uniform high signal of the fractured vertebrae gradually changed a mixed signal,stabilizing around>9-12 weeks.Statistical analysis results revealed significant differences in ADC values between>1-2 weeks,>3-5 weeks,and>9-12 weeks post-fracture(P<0.05).Significant differences in FA values were also observed between≤1 week,>1-2 weeks,>3-5 weeks,>12 weeks,and>9-12 weeks post-fracture(P<0.05).Furthermore,ADC and FA values between the fractured and normal vertebrae also showed significant differences within the first 12 weeks post-fracture(P<0.05).Conclusion The T2WI-SPAIR sequence demonstrates specific patterns of morphological and signal changes dur-ing the recovery process of fractured vertebrae.Changes in DTI parameters,including ADC and FA values,in self-comparison within the fracture zone and comparison with normal regions,follow certain patterns.These findings can provide reliable imaging evidence for clinicians to make treatment decisions and estimate the time of vertebral injury.