BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

Objective:To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism.Methods:Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of YTHDF2 mRNA and perform pathway enrichment analysis. Patients with cervical lesions diagnosed by thinprep cytologic test in Gynecological Outpatient Department of Maternal and Child Health Hospital in Jiexiu, Shanxi Province, were selected as the research subjects. Data of cervical lesions and cervical exfoliated cells were collected. HPV infection status was detected by flow-through hybridization, and the expression of YTHDF2 mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of YTHDF2 in cervical lesions and the mediating role of HPV infection in the relationship between YTHDF2 and squamous intraepithelial lesion (SIL) were evaluated. YTHDF2-related genes were screened from multiple datasets in the GEO and ENCORI databases, and their expression, immune infiltration, and survival analysis were performed to assess the association between YTHDF2 and prognosis. Results:Compared with normal cervical tissue, YTHDF2 was highly expressed in cervical lesion tissue ( P<0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that YTHDF2 was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that YTHDF2 might be related to HPV infection and other signaling pathways. In the mediation analysis, χ2 test results showed that the expression level of YTHDF2 was significantly different among groups ( χ2=22.47, P<0.001). Trend χ2 test further showed that the expression level of YTHDF2 was upregulated with the degree of cervical precancerous lesions (trend χ2=10.26, P=0.001). Multivariate logistic regression analysis indicated that high YTHDF2 expression increased the risk of low-grade squamous intraepithelial lesions ( OR=3.15, 95% CI: 1.93-5.15) and high-grade squamous intraepithelial lesions ( OR=1.85, 95% CI: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between YTHDF2 and SIL, accounting for 32.02% of the total effect. Twelve YTHDF2 related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that YTHDF2 and related genes KLF4, E2F3 and HOXC6 were associated with immune infiltration (all P<0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of KLF4 ( HR=0.53, 95% CI: 0.30-0.94) and high expression of RHOB ( HR=1.80, 95% CI: 1.04-3.13) were risk factors for the prognosis of cervical cancer. Conclusion:YTHDF2 is highly expressed in cervical lesions and may have been involved in the regulation of HPV infection-related pathways and its downstream related genes are related to immune infiltration and prognosis of cervical cancer, providing a theoretical basis for the study of mechanisms related to cervical lesions.

Objective:To investigate the role of YTHDF2 in cervical lesions and its potential molecular mechanism.Methods:Gene expression data of cervical tissue were obtained from the GEO database to analyze the expression of YTHDF2 mRNA and perform pathway enrichment analysis. Patients with cervical lesions diagnosed by thinprep cytologic test in Gynecological Outpatient Department of Maternal and Child Health Hospital in Jiexiu, Shanxi Province, were selected as the research subjects. Data of cervical lesions and cervical exfoliated cells were collected. HPV infection status was detected by flow-through hybridization, and the expression of YTHDF2 mRNA was detected by reverse transcription real-time polymerase chain reaction. The expression of YTHDF2 in cervical lesions and the mediating role of HPV infection in the relationship between YTHDF2 and squamous intraepithelial lesion (SIL) were evaluated. YTHDF2-related genes were screened from multiple datasets in the GEO and ENCORI databases, and their expression, immune infiltration, and survival analysis were performed to assess the association between YTHDF2 and prognosis. Results:Compared with normal cervical tissue, YTHDF2 was highly expressed in cervical lesion tissue ( P<0.05). A total of 3 672 differentially expressed genes were screened from the dataset GSE49339. Gene Ontology analysis showed that YTHDF2 was mainly involved in transcription regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that YTHDF2 might be related to HPV infection and other signaling pathways. In the mediation analysis, χ2 test results showed that the expression level of YTHDF2 was significantly different among groups ( χ2=22.47, P<0.001). Trend χ2 test further showed that the expression level of YTHDF2 was upregulated with the degree of cervical precancerous lesions (trend χ2=10.26, P=0.001). Multivariate logistic regression analysis indicated that high YTHDF2 expression increased the risk of low-grade squamous intraepithelial lesions ( OR=3.15, 95% CI: 1.93-5.15) and high-grade squamous intraepithelial lesions ( OR=1.85, 95% CI: 1.01-3.39). Mediation effect analysis revealed a partial mediating effect of HPV infection between YTHDF2 and SIL, accounting for 32.02% of the total effect. Twelve YTHDF2 related genes were screened by the intersection of multiple datasets. The immune infiltration analysis results showed that YTHDF2 and related genes KLF4, E2F3 and HOXC6 were associated with immune infiltration (all P<0.05). Multivariate Cox proportional hazard regression model analysis showed that low expression of KLF4 ( HR=0.53, 95% CI: 0.30-0.94) and high expression of RHOB ( HR=1.80, 95% CI: 1.04-3.13) were risk factors for the prognosis of cervical cancer. Conclusion:YTHDF2 is highly expressed in cervical lesions and may have been involved in the regulation of HPV infection-related pathways and its downstream related genes are related to immune infiltration and prognosis of cervical cancer, providing a theoretical basis for the study of mechanisms related to cervical lesions.

Objective:To explore the genetic basis for a fetus featuring oligodactyly.Methods:A fetus with hand deformity identified by ultrasound at the Maternal and Child Health Care Hospital of Hubei Province on October 20, 2018 was selected as the study subject. Clinical information and ultrasonographic finding of the pregnant woman were collected. Following elected abortion, umbilical cord and peripheral venous blood samples of the couple were collected for the extraction of genomic DNA. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing.Results:Ultrasonographic examination at 30 + 2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd ~ 5th fingers, whilst its left hand had appeared to be normal. By CNV-seq, no pathogenic or likely pathogenic copy number variation (CNV) (> 100 kb) was detected in the fetus. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene. The variant has not been recorded in the population databases, and was predicted to be deleterious by several bioinformatics software and evolutionarily conserved based on multiple sequence alignment analysis. Sanger sequencing showed that neither parent has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The fetus was diagnosed with Cornelia de Lange syndrome, for which the novel heterozygous c.3298G>A variant of the SMC3 gene may be accountable.

Objective To investigate the effect of dioscin on uric acid(UA)-induced oxidative stress injury of human renal tubular epithelial cells(HK-2)and its molecular mechanism.Methods HK-2 cells were cultured and divided into four groups:blank group(normal group),model group(uric acid-stimulation modeling),condition control group(UA+DMSO)and dioscin group(UA+dioscin).Oxidative stress injury model was induced by UA in HK-2 cells.Cells viability was detected by CCK-8.ROS level was detected by flow cytometry.Real-time PCR was used to detect the expressions of glycogen synthase kinase 3β(GSK3β),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)at mRNA level,and Western Blot was used to detect the expressions of phosphorylated glycogen synthesis kinase 3β(p-GSK3β),GSK3β,Nrf2 and HO-1 at protein level.Results After stimulation by UA,HK-2 cells viability was obviously decreased,and ROS level was significantly increased(all P＜0.001).When treated with dioscin,HK-2 cells viability was obviously increased,and the ROS level of HK-2 cells was significantly decreased(all P＜0.001).The expressions of Nrf2 and HO-1 decreased at the protein and mRNA levels after stimulation with UA.But the expressions of Nrf2 and HO-1 significantly increased after treated with dioscin(all P＜0.001).Compared with the blank group,the p-GSK3β/GSK3β ratio in the model group decreased significantly at the protein level,but the p-GSK3β/GSK3β ratio increased after treated with dioscin(all P＜0.001).Conclusion Dioscin can alleviate UA-induced oxidative stress injury in HK-2 cells.The mechanism might be that dioscin can promote phosphorylation of GSK3β,and activate Nrf2/HO-1 pathway.

Objective:To investigate the correlation between serum insulin-like growth factor 1 (IGF-1), thyroid stimulating hormone (TSH), degree of insulin resistance and thyroid nodule imaging reporting and data system (TI-RADS) grading in patients with type 2 diabetes mellitus (T2DM).Methods:The clinical data of 120 patients with T2DM from February 2020 to November 2021 in Kunshan Hospital of Integrated Traditional Chinese and Western Medicine were retrospectively analyzed. Among them, 56 patients had no thyroid nodules (non-thyroid nodule group), all patients were TI-RADS grade 1; 64 patients had thyroid nodules (thyroid nodule group), including 7 cases of TI-RADS grade 2, 12 cases of TI-RADS grade 3, 20 cases of TI-RADS grade 4, and 25 cases of TI-RADS grade 5. The levels of IGF-1 and TSH were measured by automated biochemical analyzer, the homeostatic model assessment insulin resistance index (HOMA-IR) was calculated. Spearman method was used for correlation analysis; multivariate Logistic regression was used to analyze the independent risk factors of TI-RADS grading in patients with T2DM combined with thyroid nodules; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of IGF-1, TSH and HOMA-IR in predicting TI-RADS grading in patients with T2DM combined with thyroid nodules.Results:The IGF-1, TSH and HOMA-IR in thyroid nodule group were significantly higher than those in non-thyroid nodule group: (185.35 ± 45.08) ng/L vs. (168.36 ± 30.25) ng/L, (2.98 ± 0.85) mU/L vs. (2.69 ± 0.35) mU/L and 3.25 ± 0.75 vs. 2.95 ± 0.44, and there were statistical differences ( P<0.05 or <0.01). In patients with T2DM combined with thyroid nodules, with the increase of TI-RADS classification, the IGF-1, TSH and HOMA-IR gradually increased, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that the levels of IGF-1, TSH and HOMA-IR were positive correlation with TI-RADS grading ( r = 0.918, 0.906 and 0.920; P<0.05). Multivariate Logistic regression analysis result showed that the IGF-1, TSH and HOMA-IR were independent risk factors for TI-RADS grading in patients with T2DM combined with thyroid nodule ( OR = 1.684, 1.044 and 1.851; 95% CI 0.674 to 6.665, 0.032 to 0.055 and 1.212 to 2.298; P<0.01 or <0.05). ROC curve analysis result show that the area under the curve of IGF-1, TSH and HOMA-IR for predicting the TI-RADS grading patients with T2DM combined with thyroid nodule were 0.946, 0.983 and 0.975, with all sensitivity of 100.00%, and specificity of 82.14%, 91.07% and 89.29%. Conclusions:There is a correlation between IGF-1, TSH, HOMA-IR and TI-RADS grading in patients with T2DM combined with thyroid nodule, which has some guiding value for clinical monitoring of thyroid nodule changes.