OBJECTIVE: To evaluate the effects of posterior cruciate ligament(PCL) resection on soft tissue elasticity and knee stability in total knee arthroplasty(TKA). METHODS: Six adult cadaveric knee specimens (involving 10 knees) were included in the study. With the assistance of the robotic system(TiRobot Recon, TINAVI, Beijing), total knee arthroplasty (TKA) was performed sequentially using cruciate retaining (CR) prostheses and posterior stabilizing (PS) prostheses. Between the two surgical procedures, the femoral and tibial osteotomy surfaces were not altered;only the posterior cruciate ligament (PCL) was resected and the intercondylar fossa was treated. After installing the femoral trial component, a soft tissue balance solver was used to apply tension ranging from 30 N to 90 N in 5 N increments at 0°, 10°, and 90° of knee flexion. Meanwhile, the medial and lateral joint gaps were measured synchronously. Based on the tension-gap coupling data, the equivalent elastic coefficients of the medial and lateral soft tissue sleeves at different knee flexion angles, as well as the range of the joint line convergence angle (JLCA) under fixed varus-valgus stress, were calculated. Additionally, the gap balance status under 80 N of tension was analyzed. Self-control comparisons of each indicator were conducted before and after PCL resection to analyze the change patterns. RESULTS: After PCL resection, in the fully extended position (knee flexion 0°). The medial equivalent elastic coefficient was 32.2 (25.7, 63.3) N·mm^-1 for the CR prosthesis and 27.7 (22.0, 51.9) N·mm^-1 for the PS prosthesis, and the statistically significant difference (P=0.013). The range of JLCA was 0.41°(0.26, 0.55)° for the CR prosthesis, which was smaller than 0.75° (0.40, 0.98)° for the PS prosthesis, and the difference was statistically significant(P=0.041). At 90° of knee flexion, the medial joint gap was 10.7(10.1, 11.7) mm for the CR prosthesis, which was smaller than 12.1(10.9, 15.1) mm for the PS prosthesis, with a statistically significant difference(P=0.011). No statistically significant differences were observed in other joint gaps. CONCLUSION PCL resection reduces the rigidity of the medial soft tissues in the fully extended knee and increases the medial joint gap in the flexed position, thereby affecting knee stability and balance. This finding suggests that PS and CR prostheses may require different morphological designs, and there should be differences in indications and osteotomy strategies between CR-TKA and PS-TKA. CR-TKA is more suitable for patients with preoperative medial soft tissue laxity.
Humans ; Posterior Cruciate Ligament/physiopathology* ; Knee Joint/physiopathology* ; Arthroplasty, Replacement, Knee ; Elasticity ; Male ; Female ; Middle Aged ; Aged ; Biomechanical Phenomena ; Adult

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To explore the evaluation value of shear wave elastography(SWE)parameters combined with gamma-Glutamyltransferase(GGT)and aspartate aminotransferase(AST)/alanine aminotransferase(ALT)for the severity of cirrhosis patients.Methods:96 cirrhosis patients who were admitted to Dafang County People's Hospital from January 2022 to October 2024 were selected,they were divided into control group(n=65,Child-Push A and B-grade)and an observation group(n=31,Child-Push c-grade)according to Child-Push grade.All cirrhosis patients underwent SWE examination,serum GGT levels,AST/ALT in cirrhosis patients were detected.SWE parameters(shear wave velocity,elastic modulus)and serum GGT levels,AST/ALT were compared between two groups,Pearson correlation analysis was applied to investigate the correlation between SWE parameters,serum GGT,AST/ALT,and the severity of cirrhosis.The receiver operating characteristic(ROC)curve was used to analyze the value of SWE parameters,serum GGT,AST/ALT individual and combined assessment for evaluating Child-Push c-grade cirrhosis.Delong test was used to compare the area under the ROC curve(AUC)of SWE parameter combination,serum GGT and AST/ALT combination,and SWE parameter and serum GGT,AST/ALT combination in evaluating Child-Push c-grade cirrhosis.Results:Compared with the control group,the observation group had faster shear wave velocity and higher elastic modulus(P＜0.05).The AUC values of shear wave velocity and elastic modulus individual and combined assessment were 0.712,0.739,and 0.845,respectively.Compared with the control group,the observation group had higher serum GGT,AST,ALT levels,and AST/ALT(P＜0.05).The AUC values of serum GGT,AST/ALT individual and combined assessment were 0.664,0.714,and 0.790,respectively.SWE parameters,serum GGT levels,AST/ALT were positively correlated with the severity of cirrhosis(P＜0.05).The AUC of SWE parameter combined with serum GGT and AST/ALT assessment was 0.923,significantly higher than SWE parameter combined and serum GGT and AST/ALT combined(z=2.731,2.924,both P＜0.05).Conclusion:Patients with more severe cirrhosis has a faster shear wave velocity,higher elastic modulus,and higher serum GGT levels and AST/ALT.The combined detection above indicators has good application value in evaluating the degree of cirrhosis.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective:To explore the evaluation value of shear wave elastography(SWE)parameters combined with gamma-Glutamyltransferase(GGT)and aspartate aminotransferase(AST)/alanine aminotransferase(ALT)for the severity of cirrhosis patients.Methods:96 cirrhosis patients who were admitted to Dafang County People's Hospital from January 2022 to October 2024 were selected,they were divided into control group(n=65,Child-Push A and B-grade)and an observation group(n=31,Child-Push c-grade)according to Child-Push grade.All cirrhosis patients underwent SWE examination,serum GGT levels,AST/ALT in cirrhosis patients were detected.SWE parameters(shear wave velocity,elastic modulus)and serum GGT levels,AST/ALT were compared between two groups,Pearson correlation analysis was applied to investigate the correlation between SWE parameters,serum GGT,AST/ALT,and the severity of cirrhosis.The receiver operating characteristic(ROC)curve was used to analyze the value of SWE parameters,serum GGT,AST/ALT individual and combined assessment for evaluating Child-Push c-grade cirrhosis.Delong test was used to compare the area under the ROC curve(AUC)of SWE parameter combination,serum GGT and AST/ALT combination,and SWE parameter and serum GGT,AST/ALT combination in evaluating Child-Push c-grade cirrhosis.Results:Compared with the control group,the observation group had faster shear wave velocity and higher elastic modulus(P＜0.05).The AUC values of shear wave velocity and elastic modulus individual and combined assessment were 0.712,0.739,and 0.845,respectively.Compared with the control group,the observation group had higher serum GGT,AST,ALT levels,and AST/ALT(P＜0.05).The AUC values of serum GGT,AST/ALT individual and combined assessment were 0.664,0.714,and 0.790,respectively.SWE parameters,serum GGT levels,AST/ALT were positively correlated with the severity of cirrhosis(P＜0.05).The AUC of SWE parameter combined with serum GGT and AST/ALT assessment was 0.923,significantly higher than SWE parameter combined and serum GGT and AST/ALT combined(z=2.731,2.924,both P＜0.05).Conclusion:Patients with more severe cirrhosis has a faster shear wave velocity,higher elastic modulus,and higher serum GGT levels and AST/ALT.The combined detection above indicators has good application value in evaluating the degree of cirrhosis.

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of chlorogenic acid,mulberroside A,dihydromorin,oxyresveratrol,quercetin,kaempferol,mulberrofuran G,kuwanon G,sanggenon C,sanggenone D and morusin in Mori Cortex.METHODS The analysis was performed on a 35 ℃ thermostatic Brownlee SPP C18 column ( 2.1 mm × 100 mm,2.7 μm ),with the mobile phase comprising of acetonitrile ( containing 0.1％ formic acid)-5 mmol/L ammonium acetate flowing at 0.5 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Eleven constituents showed good linear relationships within their own ranges (R2>0.9950),whose average recoveries were 94.53％-103.58％ with the RSDs of 2.51％-6.92％.Kaempferol was not detected in 18 batches of medicinal materials,oxyresveratrol,quercetin,mulberrofuran G,kuwanon G and morusin mainly existed in the outer crude bark,and mulberroside A content demonstrated obvious difference in different producing areas of medicinal materials.CONCLUSION This stable,rapid and sensitive method can be used for the quality control of Mori Cortex.

This study was aimed at understanding the Blastocystis,Enteroc ytozoon bieneusi,Cryptosporidium spp.,Gi-ardia duodenalis,and Pentatrichomonas hominis infection status in Chinese Milu deer(Elaphurus davidianus)in various prov-inces of China.A total of 81 fecal samples were collected from Beijing,Inner Mongolia,Hebei,and Hubei.PCR was used to detect the protozoans,and their subtypes and zoonoticity were determined through sequence and phylogenetic analyses.PCR re-sults indicated an infection prevalence of 40.74％,19.75％,and 8.64％for Blastocystis,E.bieneusi,and Cryptosporidium spp.,respectively,whereas G.duodenalis and P.hominis was not detected.Only one subtype of Cryptosporidium spp.(Cryptosporidium deer genotype)was detected.Four E.biene-usi genotypes were detected:HLJD-V,MWC-d1,BEB6,and CGC2.Five Blastocystis ST types were found:ST10,ST14,ST21,ST23,and ST25.Cryptosporidium spp.,E.bieneusi,and Blastocystis infections were prevalent,and zoonotic subtypes or genotypes of E.bieneusi and Blastocystis were i-dentified.The prevention and control of intestinal protozoa in Chinese Milu deer would support population health and is im-portant for public health.