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 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 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 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 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 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.

Objective:To investigate the application value of enhanced recovery after surgery (ERAS) in perioperative period of laparoscopic sleeve gastrectomy (LSG).Method:The retrospective cohort study was conducted. The clinical data of 1 181 patients undergoing LSG in the Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine from January 2021 to December 2023 were collected. There were 242 males and 939 females, aged (31±8)years. Of 1 181 patients, 598 cases receiving routine perioperative care were divided into the control group, and 583 cases receiving perioperative care with ERAS were divided into the ERAS group. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between the groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney rank sum test was used for comparison between the groups. Count data were expressed as absolute numbers or percentages, and the chi-square test or Fisher exact probability were used for comparison between the groups. Repeated measurement data were analyzed using the repeated ANOVA, with baseline scores as covariates. Simple effects analysis was conducted in case of interaction, and multiple comparisons were adjusted using the Bonferroni method. Results:(1) Postoperative outcomes. The numerical rating scale (NRS) scores for pain at immediate return to the ward and on the third postoperative mornings changed from 5.35±0.93 to 2.57±0.83 in the control group, versus changed from 3.15±0.93 to 0.70±0.65 in the ERAS group, showing significant difference between the two groups ( Ftime=66.58, Fgroup=1 765.85, Finteraction=6.90, P<0.05). After adjusting NRS scores for pain at immediate return to the ward as the baseline, results of simple effects analysis showed that on the third postoperative mornings, the NRS scores in the ERAS group were lower by 1.89, 1.53, and 1.76 respectively compared to the control group ( P<0.05). Cases with nausea at immediate return to the ward and on the third postoperative mornings changed from 497 to 97 in the control group, versus changed from 198 to 11 in the ERAS group, showing signifi-cant difference between the two groups ( χ2=294.45, 398.76,209.39, 73.00, P<0.05). Cases with vomiting at immediate return to the ward and on the third postoperative mornings changed from 243 to 41 in the control group, versus changed from 51 to 2 in the ERAS group, showing significant difference between the two groups ( χ2=160.54, 149.37, 71.76, 35.69, P<0.05). The duration of postoperative hospital stay was (3.22±0.65)days in the control group, versus (2.17±0.49)days in the ERAS group, showing a significant difference between the two groups ( t=-11.89, P<0.05). (2) Complications. The incidence of cases with dehydration within postoperative 30 days was 0.50%(3/598) in the control group, versus 0.69%(4/583) in the ERAS group, showing no significant difference between the two groups ( P>0.05). None of patient in the control group and the ERAS group experienced bleeding, gastric leakage, intra-abdominal infection, and no patient had unplanned secondary surgery within postoperative 30 days. Conclusions:ERAS in perioperative period of LSG are safe and feasible. Compared to routine care, ERAS can significantly reduce postoperative pain, decrease the incidence of postoperative nausea and vomiting, shorten the postoperative hospital stay, and do not increase the rate of postoperative complications or unplanned secondary surgeries within postoperative 30 days.