Objective To systematically identify key risk biomolecules associated with the diagnosis of prostate cancer using multi-omics analysis methods, and to explore potential drug intervention targets. Methods Based on prostate cancer genome-wide association study data, GTEx v8 expression quantitative trait locus data, and The Cancer Genome Atlas database, this study screened for differentially expressed genes associated with prostate cancer pathogenesis through transcriptome imputation, summary data-based Mendelian randomization (SMR) analysis, colocalization analysis, and differential expression analysis.The identified differentially expressed genes were subjected to gene ontology analysis, single-cell RNA sequencing analysis, and correlation analysis with immune cell infiltration levels.Mendelian randomization (MR) was employed to investigate immune pathways and circulating metabolites associated with prostate cancer diagnosis.Potential drug targets for prostate cancer were screened using SMR analysis. Results Four differentially expressed genes associated with prostate cancer were identified, among which BHLHA15 (OR=1.08) was found to be associated with prostate cancer risk for the first time. MR analysis revealed that immune cell surface molecules and the inflammatory cytokine interleukin-17A (IL-17A) (OR=1.25) were risk factors for prostate cancer.MR analysis also indicated that higher levels of sebacate (OR=1.05) and cystine disulfide (OR=1.11) were associated with an increased risk of prostate cancer.Drug target analysis screened 14 potential target genes, among which high expression of OPRL1 was significantly correlated with poorer disease-free survival in prostate cancer patients (HR=2.00, P=0.024). Conclusion This study identified biomolecules associated with prostate cancer pathogenesis through multi-omics analysis, which may help deepen the clinical understanding of the pathogenic mechanisms underlying prostate cancer and reveal potential drug targets.

Objective: To assess the current status of knowledge, attitude, and practice (KAP) regarding health protection against air pollution among primary school students in China, and to analyze the impacts of fine particulate matter (PM 2.5 ) exposure, family, and individual factors on KAP levels, so as to provide empirical basis for implementing targeted interventions. Methods: Using stratified cluster random sampling method, a questionnaire survey was conducted among 19 297 primary school students from third to fifth grade across 30 provinces (autonomous regions and municipalities directly under the central government) in China in 2024. The questionnaire was developed based on the Technical Guidelines for the Assessment of Civic Environmental and Health Literacy (Trial), and encompasses three dimensions:knowledge, attitude, and practice. Spearman correlation analysis, Chi-square test, multivariate Logistic regression, and Bootstrap mediation effect test was applied for data analysis. Results: The overall mean KAP score for health protection against air pollution among primary school students was (79.73±13.53), with an adequacy rate of 80.47% ( n =15 528). The dimension scores for knowledge, attitude, and practice were (41.34±8.01, 16.43± 2.61 ), and (21.97±5.71), respectively. Knowledge was positively correlated with attitude and practice, and attitude was positively correlated with practice ( r =0.51, 0.35, 0.32, all P <0.01). Multivariate Logistic regression showed that the northeast region ( OR =2.36, 95% CI =2.02-2.75), having parents with a bachelor s degree or higher ( OR =4.76, 95% CI =2.71-8.37), living with both parents ( OR =1.33, 95% CI =1.15-1.55), being in the fifth grade ( OR =1.22, 95% CI =1.11-1.33), outdoor PM 2.5 level exceeding standard limits at the survey site ( OR =1.25, 95% CI =1.16-1.34), history of allergy ( OR =1.47, 95% CI =1.31-1.64), and wearing masks during heavily polluted weather ( OR =1.19, 95% CI =1.07-1.31) were promoting factors for KAP adequacy rate (all P <0.05). Conversely, obesity was a detrimental factor ( OR =0.78, 95% CI =0.69-0.88, all P <0.05). Conclusions Primary school students in China exhibit a favorable KAP level regarding health protection against air pollution, though regional, familial, and individual disparities persist. Exposure to PM 2.5 levels exceeding standard limits exerts a direct positive effect on enhancing health protection literacy. Future efforts should focus on the western region, families with lower educational attainment children to implement tailored, stratified interventions.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective:To explore the effect of scalp electroacupuncture (EA) on central pain sensitization in rats with knee osteoarthritis (KOA).Methods:Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into a blank control group, a model group, an electroacupuncture (EA) group and a sham EA group, each of 8. All of the rats except those in the control group had KOA induced through intra-articular monosodium iodoacetate injections in the right knee. Two weeks later the EA group rats began receiving daily head EA sessions 6 days/week for 2 weeks. The sham EA group received identical but non-therapeutic stimulation. The blank control and model groups received no EA intervention. Before the modelling and 3, 7, 14, 21 and 28 days later, all of the rats completed bipedal balance pain tests and mechanical allodynia evaluations. After the testing on day 28, all of the rats were euthanized for molecular analyses. Western blotting and immunohistochemistry were performed to examine protein expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and cannabinoid receptor type 1 (CB1R) in both the periaqueductal gray (PAG) matter and spinal dorsal horns (SDHs). Serum levels of substance P (SP) and 5-hydroxytryptamine (5-HT) were also quantified using enzyme-linked immunosorbent assays.Results:Three days after successful modeling, the average weight-bearing capacity of the right hind limb in the model, sham EA and EA groups was significantly lower than that of the blank controls. It reached its lowest level on the 14th day after modeling. Concurrently, the pain responses in those three groups were significantly higher than among the controls, also peaking on the 14th day after modeling. After two weeks of electroacupuncture, the electroacupuncture group showed significant improvement in both right hind limb weight-bearing capacity and pain response compared to the model group. Meanwhile, the levels of BDNF and TrkB protein in the periaqueductal gray matter were significantly higher in the model group than among the blank controls, while the electroacupuncture group exhibited significantly reduced expression of BDNF and TrkB proteins compared to the model group, along with significantly increased CB1R protein expression. The model group showed significantly elevated expression of both BDNF and TrkB proteins in the spinal dorsal horn compared to the blank control group, while there were significant differences between the EA and model groups in the expression of BDNF, TrkB and CB1R proteins. Immunohistochemical analysis on day 28 revealed that the EA group had significantly fewer BDNF- and TrkB-positive cells in the PAG compared to the model group, with significantly more CB1R-positive cells. In the SDH, the model group exhibited significantly increased numbers of BDNF- and TrkB-positive cells compared to the blank control group, whereas significant differences were found between the EA and blank control groups in the numbers of BDNF-, TrkB- and CB1R-positive cells. Serum analysis on day 28 demonstrated that substance P and 5-hydroxytryptamine levels in the model, sham EA and EA groups were significantly higher than in the blank control group, on average. However, no significant differences were observed in serum SP and 5-HT levels between the EA and model groups.Conclusions:Scalp EA significantly alleviates central pain sensitization in KOA, at least in rats, potentially by suppressing BDNF and TrkB expression while upregulating CB1R expression in the PAG matter and the SDH.

Objective:To analyze the epidemiological and clinical characteristics of pertussis cases identified through active surveillance.Methods:Active surveillance for pertussis was conducted in three sentinel hospitals in Yiwu, Zhejiang Province, and Yongcheng, Henan Province. The study population included cases that met the surveillance case definition and sought medical care at outpatient/emergency departments or were hospitalized between June 1, 2021, and May 31, 2022. Samples were collected for bacterial culture and PCR detection. Case information and clinical data were collected. Differences in rates were assessed using the chi-square test or Fisher's exact probability test, and the differences in cough time were compared using the Mann-Whitney U test. Results:Among 1 423 cases of pertussis surveillance, the positive rate of pertussis was 28.11% (400/1 423), with a median age of 5 years (interquartile range: 2, 8). The positive rate in Yongcheng, Henan Province, and Yiwu, Zhejiang Province were 39.27% (216/550) and 21.08% (184/873), respectively; the positive rate of pertussis was highest in July 2021, and the highest positive rate of pertussis was among those aged 10-14. The positive rate of pertussis in hospitalized cases was higher than in outpatient/emergency cases (26.68%) ( χ2=4.16, P=0.041). Among the 400 laboratory test-positive cases, the highest proportion of atypical symptom cases was in adults aged 20-59 (43.33%, 13/30). The specificity rates of apnea and worsening nocturnal cough in monitored cases under 3 months of age were 100.00% and 73.81%, respectively. Among monitored cases aged 3 months to 9 years, the proportions of symptoms including worsening nighttime cough (63.00%) and night sweats (4.59%) in test-positive cases were significantly higher than those in the test-negative group (47.77% and 0.56%, respectively), with statistically significant differences (both P<0.05). The specificity rates of worsened nighttime coughing and night sweats were 52.23% and 99.44%, respectively. Conclusions:The active surveillance results for pertussis showed that the 10-14 age group exhibited the highest positivity rate. Active surveillance enhanced the detection rate of pertussis. Among laboratory-confirmed cases, the proportion of atypical symptoms was the highest in adults, suggesting that laboratory testing should be combined to diagnose programs of pertussis. For infants under 3 months, worsening nighttime cough and apnea increase the diagnostic specificity, while for individuals aged 3 to 9 years old, worsening nighttime cough and night sweats increase the diagnostic specificity.

This article reviews the progress of clinical research on abnormal sounds after ceramic-on-ceramic total hip arthroplasty, with a focus on analyzing the differences between the third-generation and fourth-generation ceramic prostheses. Abnormal sounds generally refer to high-pitched audible sounds (such as creaking, clicking, etc.) during hip joint movement after surgery, which are considered possible precursors to prosthesis fragmentation (for example, patients with abnormal sounds have more ceramic particles in the joint fluid, and some are accompanied by prosthesis fragmentation). The fundamental frequency of abnormal sounds in the third-generation ceramic prostheses ranges from 400 to 7 500 Hz (approximately 1 500 Hz in males and 2 500 Hz in females), while the acoustic characteristics of the fourth-generation ones remain unclear. The reported occurrence time of abnormal sounds varies significantly among different studies, with an average of 6.4 to 40 months after surgery. This variation may be influenced by patient characteristics, surgical technique, and prosthesis type. Abnormal sounds are considered a possible early indicator of prosthesis fragmentation; for instance, higher concentrations of ceramic particles have been detected in the synovial fluid of affected patients, and some cases have been accompanied by prosthesis fracture. The incidence of abnormal sounds with the fourth-generation prostheses ranges from 3.8% to 46.6% (with a follow-up period exceeding 10 years), while the third-generation shows rates of 0% to 19.7% with no difference between the two generations. Although the fourth-generation prostheses are superior to the third-generation in material toughness (flexural strength>1 380 MPa) and hardness, they still fail to solve the problem of abnormal sounds, and the incidence may increase with the extension of the follow-up time (for example, in some studies, the incidence at 10-year follow-up is higher than that at 5-year follow-up). Abnormal sounds are mostly associated with movements such as extreme flexion (e.g., squatting) and walking. Different sound properties (such as friction sound) correspond to specific inducing movements and locations, among which friction sound requires vigilance against the risk of prosthesis fragmentation. The risk factors include patient-related factors (height, weight, activity level, etc.), surgical factors (prosthesis position angle), and prosthesis-related factors (design, diameter, neck length, etc.). Proposed mechanisms include abnormal edge loading, stripe wear, femoral neck impingement, wear particle generation, and prosthesis mismatch. Adverse outcomes include decreased patient satisfaction with life, revision surgery (with an incidence of 0.2% to 4.65%), and prosthesis fragmentation. Currently, there are still controversies in research. Future studies need to focus on special patient groups, surgical techniques (such as robot-assisted surgery), and the optimization of prosthesis materials and designs (such as gradient structures and surface coatings) to reduce the incidence of abnormal sounds.

Objective:To construct an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with strong replication capacity，and comprehensively identify its viral phenotype and replication capacity.Methods:Using the CRF01_AE clinical isolate GX2005002，which was previously isolated from whole blood of an HIV-1-infected individual in China by our laboratory，as the parental strain，the full-length genome of the virus（9.7 kb）was divided into 5' half fragment（5.1 kb）and 3' half fragment（4.6 kb）for amplification. The proviral DNA was used as a template to amplify the virus genome，which was then ligated into the eukaryotic expression vector pEASY-T1. The consistency of its sequence with the parental strain sequence was identified through full-length genome sequencing and phylogenetic analysis. The replication capacity，syncytium inducibility，and cell tropism were experimentally identified to determine its phenotypic consistency with the parental strain.Results:An infectious clone of the CRF01_AE strain was successfully constructed，and its genome sequence exhibited high consistency with the sequence of the parental strain. By transfecting target cells，a derivative virus with infectious activity and replication capability was successfully rescued. The derived virus maintained phenotypic characteristics consistent with the parental strain，such as cell tropism and syncytium inducibility.Conclusion:This study successfully constructed an infectious clone of a Chinese HIV-1 CRF01_AE epidemic strain with clear background and distinct phenotype. The genomic sequence and viral phenotypic characteristics of the derived virus are basically consistent with the parental strain，providing strong representation of the original isolate and serving as a powerful tool for research on the correlation between the genetic characteristics，viral phenotype，and pathogenicity of HIV-1 CRF01_AE strains.

Objective:To explore the efficacy and feasibility of hypomethylating agent (HMA) as preventive therapy in children with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study. Data from 173 children who underwent allo-HSCT for high-risk AML at Children′s Hospital of Soochow University between August 2019 and April 2023 were analyzed. Participants were categorized into a trial group receiving HMA and a control group. Further classification was based on HMA courses:≥4 and <4 courses. The efficacy and safety of HMA preventive treatment after allo-HSCT were evaluated. Survival analysis was performed using the Kaplan-Meier method with Log-Rank testing, the Fine-Gray model was used to assess cumulative relapse rates and Cox regression was used to identify prognostic factors. Adverse events during HMA were descriptively analyzed.Results:Among 173 patients, there were 100 males (57.8%) and 73 females (42.2%), with the age of 81 (34,127) months. The starting time of HMA was 123 (91, 191) d post-transplant, continuing 4.0 (3.0, 6.5) courses and the follow-up period was 24 (13, 32) months. The trial group (53 cases) showed better 2-year overall survival (OS) rate ((88.6±5.6)% vs. (76.6±4.3)%, χ 2=5.00, P=0.025) and relapse-free survival (RFS) rate ((89.2±4.7)% vs. (56.2±4.8)%, χ 2=15.75, P<0.001) than control group (120 cases). The 2-year OS rates and RFS rates were similar between ≥4 courses group (31 cases) and <4 courses group (22 cases)(both P>0.05). The cumulative relapse rate in the trial group was significantly lower ((10.8±0.2)% vs. (35.2±0.2)%, χ 2=10.84, P=0.001) than control group. Among children with molecular relapse, 8 cases (8/30, 26.7%) in the control group had hematological relapse compared to 1 case (1/2) in the trial group ( χ 2=0.81, P=0.369). The differences in incidence of acute and chronic graft-versus-host disease (GVHD) were not statistically significant (all P>0.05). Cox regression analysis revealed that minimal residual disease (MRD) positivity detected by flow cytometry before allo-HSCT and chronic GVHD were independent risk factors for OS (both P<0.05).The HMA preventive treatment was an independent protective factor for RFS, while age ≥10 years and MRD positivity detected by PCR before allo-HSCT were independent risk factors for RFS (all P<0.05). In trial group, 38 cases experienced grade 3 to 4 adverse events (71.7%). Conclusion:HMA is safe as preventive treatment in post-transplant children with high-risk AML, which can reduce the relapse risk and doesn't increase the risk of GVHD.

Objective:To evaluate the efficacy and safety of cord blood stem cell transplantation (CBSCT) in pediatric recipients with mucopolysaccharidosis type Ⅱ (MPS Ⅱ, Hunter syndrome).Methods:Clinical data of five male children with MPS Ⅱ who underwent CBSCT at the Department of Hematology, Children's Hospital of Soochow University between March 2018 and July 2023 were retrospectively analyzed. Post-transplantation clinical outcomes and enzymatic activity were observed. Literature was searched in the China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases using the keywords "mucopolysaccharidosis type Ⅱ" "MPS Ⅱ" "IDS gene" and "Hunter syndrome" in both English and Chinese. Articles describing clinical manifestations, genetic diagnosis, and hematopoietic stem cell transplantation (HSCT) in MPS II were screened.Results:All five patients were male, with a median age at diagnosis of 4.3(2.5-5.5) years and a median age at transplantation of 4.6(2.8-6.5) years. At diagnosis, all exhibited coarse facial features, hepatosplenomegaly, skeletal deformities or abnormalities, abnormal head MRI findings, and Mongolian spots; four had joint stiffness, three had valvular heart disease, and two had airway obstruction, short stature, and intellectual disability. Three recipients received single-unit cord blood, and two received double-unit cord blood. Myeloablative conditioning regimens consisted of busulfan, cyclophosphamide, anti-thymocyte globulin ± fludarabine. The median neutrophil engraftment and platelet engraftment times were 19(14-21) days and 26(15-44) days, respectively. Complete donor chimerism was achieved at 1 month post-transplantation. Complications included peri-engraftment syndrome in 5 cases, acute graft-versus-host disease (GVHD) in 2 cases (1 with grade Ⅳ skin and grade Ⅱ intestinal involvement; 1 with grade Ⅱ skin involvement), limited chronic GVHD in 1 case (moderate intestinal involvement), cytomegalovirus (CMV) infection in 3 cases, Epstein-Barr virus (EBV) infection in 1 case, and capillary leak syndrome in 1 case; all were successfully managed. At the last follow-up in December 2023, all patients were alive, and enzyme activity had normalized by 3 months post-transplantation. Most clinical symptoms and signs improved; however, neurocognitive function showed no significant improvement, and some recipients exhibited progressive brain parenchymal changes on MRI. Literature review included 7 English and 5 Chinese studies, indicating that CBSCT and other HSCT modalities can improve multi-system clinical manifestations in MPS Ⅱ children, including restoration of enzyme activity, organ function improvement (such as liver and spleen shrinkage, adenoid reduction), enhanced motor function, and stabilization of neurocognitive function. Some studies suggest superior efficacy compared with enzyme replacement therapy, particularly in delaying disease progression and improving daily living abilities.Conclusion:CBSCT effectively restores enzymatic activity and improves multi-system manifestations in children with MPS Ⅱ, although its effect on neurological symptoms remains controversial. It is a safe and feasible therapeutic option for this condition.

Objective:To evaluate the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in treating pediatric Diamond-Blackfan anemia (DBA).Method:Clinical data of five pediatric DBA recipients who underwent haplo-HSCT at the Children's Hospital of Soochow University between June 2018 and June 2023 were retrospectively analyzed. The conditioning regimen comprised a backbone protocol of fludarabine, busulfan, and rabbit anti-human thymocyte immunoglobulin (Bu+Flu+ATG), with optional cyclophosphamide, rituximab, or thiotepa. Post-transplant prophylaxis for graft-versus-host disease (GVHD) included cyclosporine A/tacrolimus combined with mycophenolate mofetil and methotrexate. Outcome measures included neutrophil and platelet engraftment times, hematopoietic reconstitution, incidence and severity of post-transplant complications, hemoglobin maintenance, and survival status. Literature was searched in CNKI, Wanfang, and PubMed using the keywords "Diamond-Blackfan anemia" "DBA" and "haplo-HSCT" in both English and Chinese.Result:The median age at transplantation was 61 months. Human leukocyte antigen (HLA) matching ranged from 5-8/10 loci. Stem cell sources included bone marrow alone (1 case), bone marrow plus peripheral blood stem cells (PBSCT, 2 cases), umbilical cord blood (CB-HSCT, 1 case), and PBSCT combined with CB-HSCT (1 case). All five recipients achieved successful engraftment with complete hematopoietic and immune reconstitution. Median neutrophil and platelet engraftment times were 11 days and 9 days, respectively, with erythroid reconstitution at 25 days post-transplant. Complications included grade IV acute GVHD (aGVHD) in one recipient, grade I aGVHD in two recipients, and chronic GVHD (cGVHD) in one recipient. Cytomegalovirus (CMV) infection occurred in three cases, and Epstein-Barr virus (EBV) infection in one case, all of which resolved with ganciclovir. No other transplant-related complications were reported. At a median follow-up of 44.8(4.8-59.2) months, all recipients were alive with sustained erythroid reconstitution and disease-free survival. Literature review (six studies) confirmed HSCT as an effective treatment for DBA, with prognosis closely related to age at transplantation, conditioning regimens, and donor selection.Conclusion:Haplo-HSCT can be considered as a viable treatment option for pediatric DBA recipients.