ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95％confidence interval[CI]:6.95-9.72,P＜0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95％CI:2.52-6.30,P＜0.000 01;MD=4.91,95％CI:3.52-6.29,P＜0.000 01;MD=5.86,95％CI:0.09-11.63,P=0.05;MD=6.90,95％CI:2.93-10.87,P=0.000 7;MD=5.03,95％CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95％CI:24.7-65.89,P＜0.0001;SMD=7.84,95％CI:6.05-9.63,P＜0.000 01;MD=2.47,95％CI:2.01-2.93,P＜0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for＜12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration＞60 minutes may be better than＜60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.

OBJECTIVE:Some studies have shown that physical exercise can effectively improve knee extensor strength and cardiorespiratory function in burn patients;some studies have also shown that physical exercise is not effective in improving respiratory function in burn patients.Improvement effects of physical exercise on physical functions(muscle function,walking function,cardiopulmonary function,and lean body mass)of burn patients were evaluated by a systematic evaluation and meta-analysis.METHODS:Based on databases including Web of Science,PubMed,Embase,Cochrane Library,CNKI,WanFang,and the Chinese Biomedical Database,literature on the improvement of physical function in burn patients through physical exercise was searched using subject headings and free terms.With muscle function,walking ability,cardiopulmonary function,and lean body mass as the primary outcome measures,a meta-analysis was conducted to compare the efficacy of physical exercise with traditional physical therapy or conventional care methods.RESULTS:A total of 38 papers were included,of which 26 papers were included in the meta-analysis,involving 1 658 patients.Meta-analysis results showed that:(1)Physical exercise significantly enhances the knee extensor strength of the dominant leg in burn patients(mean difference[MD]=8.34,95％confidence interval[CI]:6.95-9.72,P＜0.000 01),increases quadriceps strength,peak oxygen uptake,forced vital capacity and maximum ventilation volume in 1 second,and resting heart rate(standardized mean difference[SMD]=4.41,95％CI:2.52-6.30,P＜0.000 01;MD=4.91,95％CI:3.52-6.29,P＜0.000 01;MD=5.86,95％CI:0.09-11.63,P=0.05;MD=6.90,95％CI:2.93-10.87,P=0.000 7;MD=5.03,95％CI:1.45-8.61,P=0.006),and improves the 6-minute walking distance,gait parameters,and total lean body mass(MD=45.29,95％CI:24.7-65.89,P＜0.0001;SMD=7.84,95％CI:6.05-9.63,P＜0.000 01;MD=2.47,95％CI:2.01-2.93,P＜0.000 01).(2)The subgroup analysis results indicated that the improvement in knee extensor strength of the dominant leg may be better in children than in adults and better in the extra-heavy group than in the heavy group.Improvement in the 6-minute walking distance is better in children than in adults,and higher degree of burn indicates better improvement effects,with no difference from the control group for＜12 weeks.Peak oxygen uptake may be better in adults and severe burn groups than in children and moderate burn groups,resistance combined with aerobic exercise modalities may be better than aerobic exercise alone,and exercise duration＞60 minutes may be better than＜60 minutes.CONCLUSION:Physical activity is effective in improving physical function in burn patients,as evidenced by improvements in muscle strength,walking ability,cardiorespiratory fitness,and lean body mass.The quality of evidence recommended for all indicator results is moderate or below,with imprecision and inconsistency being the main factors for downgrading.Therefore,more high-quality randomized controlled trials are needed in the future to verify the reliability of the results.

The initiation of adaptive immune responses relies on the precise recognition and interpretation of antigenic information. In this process, the specific binding of T cell receptors (TCRs) to peptide-major histocompatibility complex (pMHC) molecules represents one of the key molecular events in the initiation of adaptive immune responses. Accordingly, the structural features of TCR-pMHC complexes provide a fundamental basis for dissecting antigen recognition mechanisms and support rational vaccine design, therapeutic target discovery in TCR-based immunotherapy, and TCR identification and optimization. However, experimental determination of TCR-pMHC structures remains costly, time-consuming, and limited in coverage, making computational approaches essential for rapidly obtaining reliable structural information. Computational methods for predicting the structures of TCR-pMHC complexes have advanced rapidly in recent years, driven by progress in deep learning-based modeling frameworks and the increasing availability of structural and sequence resources. Despite these developments, most existing tools do not adequately distinguish the key structural and biophysical differences between MHC class I (MHC-I) and MHC class II (MHC-II) complexes during model construction. As a consequence, their predictive performance differs substantially between class I and class II complexes. In general, structural predictions for class I complexes outperform those for class II complexes. This discrepancy may be related to several fundamental differences between the two systems, including the architecture of the peptide-binding groove, the distribution of peptide lengths, and the properties of peptide flanking residues (PFRs). Compared with MHC-I molecules, MHC-II molecules usually bind longer antigenic peptides, which typically range from 13 to 25 amino acids in length. PFRs at both termini of these peptides participate in regulating the overall conformation of TCR-pMHC class II complexes and exert a pronounced effect on the geometric and physicochemical characteristics of the TCR-pMHC binding interface. Furthermore, within the TCR recognition interface, the complementarity-determining regions (CDRs) consist of segments that differ markedly in conformational behavior. They commonly include regions that are relatively rigid and structurally stable, together with highly flexible segments exhibiting substantial conformational plasticity. These rigidity-flexibility features constitute an essential structural basis enabling TCRs to recognize diverse peptide-MHC ligands and to accommodate conformational heterogeneity at the interface. However, many current modeling tools, in an effort to enforce global conformational stability or reduce structural noise, tend to over-constrain intrinsically flexible regions. Such oversimplification may lead to inappropriate rigidification of flexible CDR loops, resulting in local structural distortions, compromised interface geometry, or even complete modeling failure for specific complexes. Against this background, the review approaches the field from the perspective of computational differences between MHC-I and MHC-II complexes. We first systematically organize and summarize available resources related to TCRs and pMHCs, including structural datasets, sequence databases, prediction tools, and benchmarking studies. We then focus on five representative tools capable of predicting both class I and class II complexes—AlphaFold2, AlphaFold3, TCRmodel2, tFold-TCR, and TCR-pHLA_ModellerS. After excluding structures present in the training sets of these tools, we constructed a benchmark dataset comprising 25 class I and 10 class II TCR-pMHC complexes in the bound state and conducted a systematic evaluation using this dataset. We first employ widely used general evaluation metrics, including All-Atom Root Mean Square Deviation (All-Atom RMSD), Backbone RMSD, Template Modeling score (TM-score), and DockQ, to assess the global conformational accuracy and interface modeling quality of class I and class II complexes. For class II complexes, we propose for the first time a peptide flanking residue deviation index, including the PFRs-Deviation Index (PFRs-DI), N-PFR-Deviation Index (N-PFR-DI), and C-PFR-Deviation Index (C-PFR-DI), to quantitatively characterize conformational deviations in PFRs. In addition, we propose the CDR conformational consistency index (CCC) designed to qualitatively evaluate the ability of prediction tools to capture TCR CDR conformational flexibility. These metrics collectively assess a tool’s ability to model both overall conformation and critical functional regions, thereby addressing the limitations of existing evaluation criteria that overemphasize global structure while inadequately capturing modeling quality in key functional areas. This establishes a unified analytical framework for MHC-I and MHC-II complexes to guide data resource selection, modeling strategy formulation, and evaluation system development. The framework further advances computational modeling and provides crucial support for multi-scale analysis of TCR-pMHC recognition mechanisms and their biological functions.

The initiation of adaptive immune responses relies on the precise recognition and interpretation of antigenic information. In this process, the specific binding of T cell receptors (TCRs) to peptide-major histocompatibility complex (pMHC) molecules represents one of the key molecular events in the initiation of adaptive immune responses. Accordingly, the structural features of TCR-pMHC complexes provide a fundamental basis for dissecting antigen recognition mechanisms and support rational vaccine design, therapeutic target discovery in TCR-based immunotherapy, and TCR identification and optimization. However, experimental determination of TCR-pMHC structures remains costly, time-consuming, and limited in coverage, making computational approaches essential for rapidly obtaining reliable structural information. Computational methods for predicting the structures of TCR-pMHC complexes have advanced rapidly in recent years, driven by progress in deep learning-based modeling frameworks and the increasing availability of structural and sequence resources. Despite these developments, most existing tools do not adequately distinguish the key structural and biophysical differences between MHC class I (MHC-I) and MHC class II (MHC-II) complexes during model construction. As a consequence, their predictive performance differs substantially between class I and class II complexes. In general, structural predictions for class I complexes outperform those for class II complexes. This discrepancy may be related to several fundamental differences between the two systems, including the architecture of the peptide-binding groove, the distribution of peptide lengths, and the properties of peptide flanking residues (PFRs). Compared with MHC-I molecules, MHC-II molecules usually bind longer antigenic peptides, which typically range from 13 to 25 amino acids in length. PFRs at both termini of these peptides participate in regulating the overall conformation of TCR-pMHC class II complexes and exert a pronounced effect on the geometric and physicochemical characteristics of the TCR-pMHC binding interface. Furthermore, within the TCR recognition interface, the complementarity-determining regions (CDRs) consist of segments that differ markedly in conformational behavior. They commonly include regions that are relatively rigid and structurally stable, together with highly flexible segments exhibiting substantial conformational plasticity. These rigidity-flexibility features constitute an essential structural basis enabling TCRs to recognize diverse peptide-MHC ligands and to accommodate conformational heterogeneity at the interface. However, many current modeling tools, in an effort to enforce global conformational stability or reduce structural noise, tend to over-constrain intrinsically flexible regions. Such oversimplification may lead to inappropriate rigidification of flexible CDR loops, resulting in local structural distortions, compromised interface geometry, or even complete modeling failure for specific complexes. Against this background, the review approaches the field from the perspective of computational differences between MHC-I and MHC-II complexes. We first systematically organize and summarize available resources related to TCRs and pMHCs, including structural datasets, sequence databases, prediction tools, and benchmarking studies. We then focus on five representative tools capable of predicting both class I and class II complexes—AlphaFold2, AlphaFold3, TCRmodel2, tFold-TCR, and TCR-pHLA_ModellerS. After excluding structures present in the training sets of these tools, we constructed a benchmark dataset comprising 25 class I and 10 class II TCR-pMHC complexes in the bound state and conducted a systematic evaluation using this dataset. We first employ widely used general evaluation metrics, including All-Atom Root Mean Square Deviation (All-Atom RMSD), Backbone RMSD, Template Modeling score (TM-score), and DockQ, to assess the global conformational accuracy and interface modeling quality of class I and class II complexes. For class II complexes, we propose for the first time a peptide flanking residue deviation index, including the PFRs-Deviation Index (PFRs-DI), N-PFR-Deviation Index (N-PFR-DI), and C-PFR-Deviation Index (C-PFR-DI), to quantitatively characterize conformational deviations in PFRs. In addition, we propose the CDR conformational consistency index (CCC) designed to qualitatively evaluate the ability of prediction tools to capture TCR CDR conformational flexibility. These metrics collectively assess a tool’s ability to model both overall conformation and critical functional regions, thereby addressing the limitations of existing evaluation criteria that overemphasize global structure while inadequately capturing modeling quality in key functional areas. This establishes a unified analytical framework for MHC-I and MHC-II complexes to guide data resource selection, modeling strategy formulation, and evaluation system development. The framework further advances computational modeling and provides crucial support for multi-scale analysis of TCR-pMHC recognition mechanisms and their biological functions.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*