OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Objective To investigate the therapeutic mechanism of Thesium chinense Turcz.(TCT)for antibiotic-associated diarrhea(AAD).Methods Network pharmacology,KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD,the key signaling pathways and the binding between the active components in TCT and the core protein targets.In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride,the effects of daily gavage of 1%carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg(n=10)on body weight and diarrhea were observed.HE staining,ELISA,16S rRNA sequencing,and Western blotting were used to examine pathologies,expression levels of IL-6 and TNF-α,changes in gut microbiota,and protein expressions of EGFR,p-EGFR,PI3K,p-PI3K,Akt,and p-Akt in the colon tissues of the mice.Results We identified a total of 66 active components of TCT and 68 core targets including EGFR,STAT3 and PIK3CA.KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway.Molecular docking showed that EGFR had the highest binding affinity with coniferin,and the EGFR-coniferin complex maintained a stable conformation at 10 ns,whose stability was also confirmed by Gibbs free energy analysis.In the mouse models of AAD,treatment with TCT significantly improved colonic tissue morphology,decreased colonic levels of TNF-α and IL-6,increased gut microbiota diversity,and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides.TCT treatment also markedly reduced protein expressions of p-EGFR,p-PI3K and p-Akt in the colon tissues of the mice.Conclusion TCT can alleviate AAD in mice by modulating gut microbiota composition,regulating the EGFR/PI3K/Akt signaling pathway,and reducing TNF-α and IL-6 expressions.

Objective To make a comparative analysis on mechancial properties of the modified cortical bone trajectory(MCBT)nailing technique using a novel variable-diameter screw and the traditional pedicle nailing technique using the cement-augmented pedicle screw(CAPS)in the L4 vertebral body.Merthods CAPS and MCBT instrumentation in the L4 vertebral body model were established by obtaining CT scan data from osteoporotic patients.The finite element method was used to compare the stability,screw axial pull-out force and lumbar spine motion under four working conditions(upper,lower,left and right loads)by using different nailing techniques.Results The axial pull-out force of the screws in MCBT group was 25.3％higher than that of the CAPS group(P＜0.05);the load-displacement ratios of the screws in MCBT group were 14.9％(P＞0.05),23.2％(P＞0.05),and 19.1％(P＜0.05)higher than those of CAPS group under the lower,left,and right working conditions,respectively;the load-displacement ratios of the screws in MCBT group were slightly lower than those of CAPS group under the upper working condition,but the differences were not statistically significant(P＞0.05);under the anterior and posterior flexion conditions,the lumbar spine motion of MCBT group was reduced by 13.3％and 2.5％,respectively,compared with CAPS group;under the left lateral bending,right lateral bending,and axial rotational conditions,the lumbar spine motion of MCBT group was improved by 69.1％,74.6％,and 118.1％,respectively,compared with CAPS group,but these differences were not statistically significant(P＞0.05).Conclusions MCBT screw was slightly better than CAPS in axial resistance to extraction force,and stability of vertebral anterior flexion under lower,left and right working conditions,and slightly weaker than CAPS in stability under upper,left lateral bending,right lateral bending,and axial rotational conditions.This study demonstrates that MCBT screw has certain advantages over CAPS,providing a pre-basic foundation for the clinical application of MCBT nailing technique for treating osteoporosis.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To make a comparative analysis on mechancial properties of the modified cortical bone trajectory(MCBT)nailing technique using a novel variable-diameter screw and the traditional pedicle nailing technique using the cement-augmented pedicle screw(CAPS)in the L4 vertebral body.Merthods CAPS and MCBT instrumentation in the L4 vertebral body model were established by obtaining CT scan data from osteoporotic patients.The finite element method was used to compare the stability,screw axial pull-out force and lumbar spine motion under four working conditions(upper,lower,left and right loads)by using different nailing techniques.Results The axial pull-out force of the screws in MCBT group was 25.3％higher than that of the CAPS group(P＜0.05);the load-displacement ratios of the screws in MCBT group were 14.9％(P＞0.05),23.2％(P＞0.05),and 19.1％(P＜0.05)higher than those of CAPS group under the lower,left,and right working conditions,respectively;the load-displacement ratios of the screws in MCBT group were slightly lower than those of CAPS group under the upper working condition,but the differences were not statistically significant(P＞0.05);under the anterior and posterior flexion conditions,the lumbar spine motion of MCBT group was reduced by 13.3％and 2.5％,respectively,compared with CAPS group;under the left lateral bending,right lateral bending,and axial rotational conditions,the lumbar spine motion of MCBT group was improved by 69.1％,74.6％,and 118.1％,respectively,compared with CAPS group,but these differences were not statistically significant(P＞0.05).Conclusions MCBT screw was slightly better than CAPS in axial resistance to extraction force,and stability of vertebral anterior flexion under lower,left and right working conditions,and slightly weaker than CAPS in stability under upper,left lateral bending,right lateral bending,and axial rotational conditions.This study demonstrates that MCBT screw has certain advantages over CAPS,providing a pre-basic foundation for the clinical application of MCBT nailing technique for treating osteoporosis.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2～3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26％ and the specificity was 83.82％.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.