This study investigated the effect of Wuling San on transforming growth factor-β1(TGF-β1)-induced fibrosis, inflammation, and oxidative stress in human renal tubular epithelial cells(HK-2) and its mechanism of antioxidant stress injury. HK-2 cells were cultured in vitro and divided into a control group, a TGF-β1 model group, and three treatment groups receiving Wuling San-containing serum at low(2.5%), medium(5.0%), and high(10.0%) doses. TGF-β1 was used to establish the model in all groups except the control group. CCK-8 was used to analyze the effect of different concentrations of Wuling San on the activity of HK-2 cells with or without TGF-β1 stimulation. The expression of key fibrosis molecules, including actin alpha 2(Acta2), collagen type Ⅰ alpha 1 chain(Col1α1), collagen type Ⅲ alpha 1 chain(Col3α1), TIMP metallopeptidase inhibitor 1(Timp1), and fibronectin 1(Fn1), was detected using qPCR. The expression levels of inflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-4(IL-4), were measured using ELISA kits. Glutathione peroxidase(GSH-Px), malondialdehyde(MDA), catalase(CAT), and superoxide dismutase(SOD) biochemical kits were used to analyze the effect of Wuling San on TGF-β1-induced oxidative stress injury in HK-2 cells, and the expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), and NAD(P)H quinone oxidoreductase 1(NQO1) was analyzed by qPCR and immunofluorescence. The CCK-8 results indicated that the optimal administration concentrations of Wuling San were 2.5%, 5.0%, and 10.0%. Compared with the control group, the TGF-β1 model group showed significantly increased levels of key fibrosis molecules(Acta2, Col1α1, Col3α1, Timp1, and Fn1) and inflammatory cytokines(TNF-α, IL-1β, IL-6, IL-8, and IL-4). In contrast, the Wuling San administration groups were able to dose-dependently inhibit the expression levels of key fibrosis molecules and inflammatory cytokines compared with the TGF-β1 model group. Wuling San significantly increased the activities of GSH-Px, CAT, and SOD enzymes in TGF-β1-stimulated HK-2 cells and significantly inhibited the level of MDA. Furthermore, compared with the control group, the TGF-β1 model group exhibited a significant reduction in the expression of Nrf2, HO-1, and NQO1 genes and proteins. After Wuling San intervention, the expression of Nrf2, HO-1, and NQO1 genes and proteins was significantly increased. Correlation analysis showed that antioxidant stress enzymes(GSH-Px, CAT, and SOD) and Nrf2 signaling were significantly negatively correlated with key fibrosis molecules and inflammatory cytokines in the TGF-β1-stimulated HK-2 cell model. In conclusion, Wuling San can inhibit TGF-β1-induced fibrosis in HK-2 cells by activating the Nrf2 signaling pathway, improving oxidative stress injury, and reducing inflammation.
Humans ; Oxidative Stress/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Fibrosis/genetics* ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Epithelial Cells/immunology* ; Inflammation/metabolism*

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

This study investigated the role of Echinococcus multilocularis vesicle-derived extracellular vesicles(EVs)con-taining emu-miR-10-5p in regulating HSC activation in vitro.Mice were injected intraperitoneally with protoscoleces to con-struct a secondary alveolar echinococcosis model,and E.multilocularis vesicles were cultured in mice and identified by PCR.The EV structure in cultured vesicle tissue was observed by transmission electron microscopy.EVs were isolated from vesicle culture supernatants through differential-ultracentrifugation,and identified by transmission electron microscopy,nanoparticle size analysis,and western blotting.The activity of HSCs treated with different EV concentrations was detected with CCK-8 assays.The expression levels of α-SMA,and collagen Ⅰ and Ⅲ were detected by RT-qPCR and western blotting after EV treatment of HSCs.Bioinformatics analysis identified the specific miRNA emu-miR-10-5p.The proliferation of HSCs was detected with EdU after overexpression of emu-miR-10-5p,and the expression levels of α-SMA,collagen Ⅰ,and collagen Ⅲ in cells were detected by RT-qPCR and western blotting.Detection of α-SMA,collagen Ⅰ,and collagen Ⅲ expression levels in HSCs was performed after EVs were extracted from the culture supernatant of vesicular tissues with emu-miR-10-5p knockdown.E.multilocularis vesicles were successfully cultured from focal material in mice,and the E.multilocularis origin was confirmed through PCR amplification of specific genes.TEM observation of culture vesicles in-dicated abundant surface vesicular structures.E.multilocularis vesicle-derived EVs were isolated by differential-ultracentrifu-gation,and confirmed by TEM to be spherical and membrane like-structures.Vesicle-derived EVs were internalized by HSCs,and promoted the proliferation and activation of HSCs.Comprehensive analysis of miRNA sequencing results revealed emu-miR-10-5p expression in E.multilocularis-infected mouse serum,metacestode tissue,E.multilocularis-derived EVs,germi-nal layer cells,and protoscoleces.Moreover emu-miR-10-5p was confirmed to be present in higher amounts in E.multilocu-laris-derived EVs,according to RT-qPCR.Further studies confirmed that overexpression of emu-miR-10-5p promoted HSC proliferation and increased α-SMA,collagen Ⅰ,and collagen Ⅲ mRNA and protein expression levels in HSCs.In contrast,EVs extracted from culture supernatants after emu-miR-10-5p knockdown in vesicles did not increase a-SMA,collagen Ⅰ,and colla-gen Ⅲ mRNA and protein expression levels.E.multilocularis vesicle-derived EVs and emu-miR-10-5p thus promote the acti-vation of HSCs.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Hepatic cystic echinococcosis is a chronic parasitic disease caused by the infection with the larvae of Echinococcus granulosus in human or animal liver tissues. As a chronic active infectious disease, tuberculous empyema mainly invades the pleural space and then causes visceral and parietal pleura thickening. It is rare to present comorbidity for hepatic cystic echinococcosis and tuberculous empyema. This case report presents a case of hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis, aiming to improve clinicians’ ability to distinguish this disorder.

Corrosive sclerosing cholangitis is a rare postoperative complication of hepatic cystic echinococcosis. Although corrosive sclerosing cholangitis is rare, it progresses rapidly and lacks effective treatments, which usually results in a poor prognosis. This case report retrospectively analyzed the treatment and diagnosis of a case with corrosive sclerosing cholangitis following surgical treatment of hepatic cystic echinococcosis, so as to provide insights into the diagnosis and treatment of corrosive sclerosing cholangitis.