Objective To explore the potential therapeutic targets and mechanisms of Shujinxi External Granules in the treatment of osteoarthritis(OA).Methods The chemical constituents and targets of Shujinxi External Granules were collected from TCMSP,TCMIP,TCMID and HERB databases,and the target genes related to OA were obtained from GEO database.Screening the overlapping targets,Cytoscape software was used to construct the"Shujinxi External Granules-compounds-OA-targets"and protein-protein interaction(PPI)networks.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the overlapping targets through DAVID database,and the compounds and proteins with the highest degree values were selected for molecular docking by using AutoDock Vina.Results There were 85 components and 915 targets were found in Shujinxi External Granules.The 4 383 targets of OA were obtained,and 248 overlapping targets were screened out between Shujinxi External Granules and OA.The key target proteins were epidermal growth factor receptor(EGFR),cyclin-dependent kinase 1(CDK1),matrix metalloproteinase 9(MMP9),and the key compounds were N-trans-feruloyltyramine,palmatine,balanophonin,aurantiamide acetate,Saroaspidin A,luteolin,schizandrin,rhynchophylline,rhynchophylline A,kaempferol,1-piperoylpiperidine.A total of 489 biological processes,162 cellular components and 87 molecular functions were obtained by using GO functional enrichment analysis,and 100 signaling pathways related to the therapeutic of Shujinxi External Granules were obtained by using KEGG pathway enrichment analysis.The molecular docking results showed that N-trans-feruloyltyramine,1-piperonoylpiperidine and rhynchophylline A had good binding ability to the key targets EGFR,CDK1 and MMP9,respectively.Conclusion The Shujinxi External Granules may bind to the key targets EGFR,CDK1,and MMP9 in the pathways in cancer,hypoxia-inducible factor 1(HIF-1)and calcium signaling pathway through the key active components,such as N-trans-feruloyltyramine,rhynchophylline A,and 1-piperoylpiperidine,to exert the therapeutic effects on OA.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

OBJECTIVE: To summarize the research and clinical application progress of foot lengthening surgery. METHODS: Relevant research literature on foot lengthening surgery in recent years at home and abroad was reviewed, and a summary was made from aspects such as the types of lengthening surgery, the types of foot diseases treated by clinical application, effectiveness, and complications. RESULTS: Bone defects and shortening deformities of the foot are relatively common clinically. As an innovative treatment method, foot lengthening surgery has gradually attracted attention, mainly including the Ilizarov technique and one-stage bone grafting lengthening surgery. The former promotes bone regeneration based on the tension-stress principle and is widely used in the treatment of calcaneal defects and congenital metatarsal brachymetatarsia, achieving good curative effects. However, there are also complications such as pin-tract infection, joint stiffness and contracture, non-union and delayed union of bone, re-fracture, and alignment deviation. The latter has a short treatment cycle, but the lengthening length is limited. Bone graft resorption and soft tissue complications are its main complications. CONCLUSION Foot lengthening surgery will develop towards the direction of personalization, intelligence, and precision. With the help of multi-center research, biological materials, and intelligent technologies, the effectiveness and safety will be further improved to better restore the function and appearance of the foot.
Humans ; Bone Transplantation/methods* ; Bone Lengthening/methods* ; Ilizarov Technique ; Osteogenesis, Distraction/methods* ; Foot Deformities/surgery* ; Postoperative Complications ; Treatment Outcome ; Foot/surgery*

Objective To explore the risk factors of respiratory failure(RF)in patients with Klebsiella pneumoniae pneumonia(KPN).Methods A total of 79 KPN patients admitted to Jilin Provincial People's Hospital from July 2023 to July 2024 were selected as subjects.Patients were divided into RF group(n=42)and non-RF group(n=37)based on RF comorbidity status.Independent risk factors for RF comorbidity were identified through univariate analysis and multivariate Logistic regression,with model predictive performance evaluated using receiver operating characteristic(ROC)curve.Results Compared to non-RF group,serum procalcitonin(PCT)levels were higher and serum albumin(ALB)and oxygenation index were lower in RF group(P＜0.05).Univariate analysis identified age,bedridden status,number of comorbidities,PCT,oxygenation index,ALB,multi-lobar infiltration,and mechanical ventilation as significant predictors of RF development in KPN patients.Multivariate Logistic analysis showed that elevated PCT levels,decreased oxygenation index,and reduced ALB were independent risk factors for RF in KPN patients,with area under the ROC curve of predictive model being 0.884.Conclusion When blood PCT is elevated,blood ALB is reduced,and the oxygenation index is decreased,the likelihood of RF in KPN patients is significantly increased.

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 explore the value and related mechanism of preoperative serum sialic acid (SA) on evaluating microvascular invasion (MVI) in patients with intrahepatic cholangiocarcinoma (ICC).Methods:A total of 91 patients who underwent surgical resection and were pathologically diagnosed with ICC from December 2020 to September 2024 at the Oriental Hepatobiliary Surgery Hospital affiliated to the Naval Medical University were included in this retrospective analysis. The patients were divided into non-MVI (41 cases) and MVI groups (50 cases). The general data and laboratory examination indexes were collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for predicting MVI. The predictive value of serum indicators for MVI was evaluated by receiver operating characteristic curves. The correlation between MVI and SA was analyzed by point-biserial correlation. ICC cells stably overexpressing β-galactoside α2, 6-sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. ST6GAL1 protein expression and mRNA expression were detected by Western blot and quantitative real-time polymerase chain reaction, respectively. Sambucus nigra (SNA) lectin fluorescence staining was used to detect α2, 6-sialylation levels on cells. Cell migration ability was assessed by wound healing and Transwell assays, and cell proliferation was evaluated by colony formation assays.Results:Compared with the non-MVI group, patients in the MVI group exhibited significantly higher levels of fibrinogen, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, SA and 5′-nucleotidase (5′-NT) (all P<0.05). Multivariate logistic regression analysis revealed that SA ( OR=1.01,95% CI 1.01-1.02, P=0.023) was the only independent predictor for MVI. The area under curve of SA in predicting MVI was 0.757 (95% CI 0.640-0.870), sensitivity 67.65%, specificity 77.78%. SA was positively correlated with MVI ( r=0.443, P<0.001). ICC cells overexpressing ST6GAL1 were featured with increased mean fluorescence intensity of SNA lectin, and increased level of α2, 6-sialylation on the cell surface (both P<0.05). The number of colonies formed by hypersialylated ICC cells was also increased ( P<0.05), and both the migration rate and the number of migrating cells were significantly higher ( P<0.05). Conclusions:Serum SA is an independent predictor for MVI in ICC patients. Hypersialylation in ICC cells is associated with higher malignancy.

Objective:To analyze the clinical outcomes of total ankle arthroplasty (TAA) using the INBONE Ⅱ prosthesis in patients ≤50 years old with end-stage ankle arthritis.Methods:A retrospective analysis was conducted of the consecutive patients who had undergone TAA using the INBONE Ⅱ prosthesis between September, 2016 and August, 2021 at Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital, Capital Medical University. There were 12 males and 16 females with an age of (46.0±4.0) years and a body mass index of (24.9±3.3) kg/m 2. The clinical outcomes recorded and compared between pre-surgery and the last follow-up were tibial articular surface (TAS) angle, talar tilt (TT) angle, tibial lateral surface (TLS) angle, ankle plantarflexion angle, ankle dorsiflexion, ankle range of motion (ROM), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, MOS item short form health survey (SF-36), foot function index (FFI), and visual analog scale (VAS) for pain. Patient satisfaction by 5-point Likert scale and complications were recorded. Results:All patients were followed up for (49.8±15.3) months. Except for plantar flexion and TAS, for all patients at the last follow-up, TT angle [0.4° (0, 0.6°)], FFI [20.0 (7.3, 48.0) points], and VAS pain score [2.0 (1.0, 2.8) points] were significantly reduced compared with the preoperative values [1.6° (0.3°, 4.4°), (99.9±40.6) points, and 6.0 (4.0, 6.8) points], while TLS angle (86.3°±2.8°), ankle dorsiflexion (13.5°±5.4°), ankle ROM (34.7°±7.9°), AOFAS ankle-hindfoot score [82.0 (74.0, 89.0) points], and SF-36 score [122.5 (112.8, 130.2) points] were all significantly higher than the preoperative values [78.9°±5.7°, 10.3°±8.0°, 31.1°±12.0°, (49.9±3.2) points, and 97.7(89.8, 101.6) points] (all P<0.05). The rate of patient satisfaction at the last follow-up was 89.3% (25/28). No serious postoperative complications occurred and no revision surgery was required. Conclusion:TAA using the INBONE Ⅱ prosthesis has shown good clinical outcomes and a high rate of patient satisfaction in younger patients ≤50 years old with end-stage ankle arthritis.

Objective:To evaluate the early-to-mid-term efficacy of supramalleolar osteotomy (SMO) in the treatment of traumatic ankle arthritis secondary to peri-ankle fracture.Methods:A retrospective study was conducted to analyze the clinical data of 29 patients who had been treated for traumatic ankle arthritis secondary to old peri-ankle fracture by SMO from March 2018 to March 2023 at Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital. There were 14 males and 15 females, 39.0 (25.0, 49.0) years in age. Types of old fracture: 4 lower tibiofibular fractures, 19 ankle fractures, and 6 pilon fractures. Surgery was conducted for 16 cases and conservative treatment for the remaining 13 cases. The interval between the old fracture and the current surgery was 10.0 (2.0, 19.5) years. The clinical efficacy was evaluated using the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS), foot function index (FFI), and visual analog scale (VAS) pain score. Imaging analysis was conducted and imaging comparisons were made between pre-surgery and post-surgery in terms of tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, talar tilt (TT) angle, and changes in modified Takakura staging. Complications were recorded. Surgical satisfaction was investigated at the final follow-up.Results:The 29 patients were followed up for 17.0 (14.0, 23.5) months. The AOFAS ankle-hindfoot score [(84.2±9.6) points], FFI [7.0 (3.0, 10.9) points], VAS pain score [2.0 (1.0, 3.0) points], and TAS angle [90.84° (86.70°, 92.50°)] at the final follow-up for all patients were significantly better than the pre-surgery values [(68.0±16.7) points, 20.9 (6.1, 29.1) points, 5.0 (2.0, 8.0) points, and 78.63° (74.30°, 85.00°)] (all P<0.05). At the final follow-up, the ankle arthritis grading did not show any significant change ( P>0.05) and there were no significant differences in TT angle or TLS angle between pre-surgery and post-surgery ( P>0.05). Incision failed to heal in 1 case, incision healing was delayed in 3 cases, and ankle arthritis progressed on imaging in 6 cases. As for patient self-assessed satisfaction, 23 cases felt very satisfactory, 4 cases quite satisfactory, and 2 cases common, giving an overall satisfaction rate of 93.1% (27/29). Conclusions:SMO has led to good early-to-mid-term efficacy in the treatment of traumatic ankle arthritis secondary to peri-ankle fracture, showing obvious pain relief and functional improvement after correction of the ankle joint alignment, limited postoperative complactions and a high rate of patient satisfaction.

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 explore the value and related mechanism of preoperative serum sialic acid (SA) on evaluating microvascular invasion (MVI) in patients with intrahepatic cholangiocarcinoma (ICC).Methods:A total of 91 patients who underwent surgical resection and were pathologically diagnosed with ICC from December 2020 to September 2024 at the Oriental Hepatobiliary Surgery Hospital affiliated to the Naval Medical University were included in this retrospective analysis. The patients were divided into non-MVI (41 cases) and MVI groups (50 cases). The general data and laboratory examination indexes were collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for predicting MVI. The predictive value of serum indicators for MVI was evaluated by receiver operating characteristic curves. The correlation between MVI and SA was analyzed by point-biserial correlation. ICC cells stably overexpressing β-galactoside α2, 6-sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. ST6GAL1 protein expression and mRNA expression were detected by Western blot and quantitative real-time polymerase chain reaction, respectively. Sambucus nigra (SNA) lectin fluorescence staining was used to detect α2, 6-sialylation levels on cells. Cell migration ability was assessed by wound healing and Transwell assays, and cell proliferation was evaluated by colony formation assays.Results:Compared with the non-MVI group, patients in the MVI group exhibited significantly higher levels of fibrinogen, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, SA and 5′-nucleotidase (5′-NT) (all P<0.05). Multivariate logistic regression analysis revealed that SA ( OR=1.01,95% CI 1.01-1.02, P=0.023) was the only independent predictor for MVI. The area under curve of SA in predicting MVI was 0.757 (95% CI 0.640-0.870), sensitivity 67.65%, specificity 77.78%. SA was positively correlated with MVI ( r=0.443, P<0.001). ICC cells overexpressing ST6GAL1 were featured with increased mean fluorescence intensity of SNA lectin, and increased level of α2, 6-sialylation on the cell surface (both P<0.05). The number of colonies formed by hypersialylated ICC cells was also increased ( P<0.05), and both the migration rate and the number of migrating cells were significantly higher ( P<0.05). Conclusions:Serum SA is an independent predictor for MVI in ICC patients. Hypersialylation in ICC cells is associated with higher malignancy.