Objective:To compare the efficacy of hip hemiarthroplasty via the fracture line approach versus modified Harding approach in the treatment of unstable intertrochanteric fractures in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 79 elderly patients with unstable intertrochanteric fractures who were admitted to Zhengzhou Orthopaedic Hospital between July 2018 and February 2024, including 17 males and 62 females, aged 80-96 years [(84.0±9.6)years]. According to the AO classification, the fractures were classified as type A2 in 61 patients and type A3 in 18. All the patients underwent hip hemiarthroplasty, 33 of whom were treated via the fracture line approach (fracture line approach group) and 46 via the modified Harding approach (modified Harding approach group). The incision length, operation duration, intraoperative blood loss, blood transfusion volume, and weight-bearing time were documented. At 1 month, 3 months after surgery and at the last follow-up, hip function and pain were assessed using the Harris hip score and visual analogue scale (VAS). Postoperative dislocation rate, fracture nonunion rate, incidence of other complications (vascular injury, neurologic impairment, prosthesis loosening, lower extremity venous thrombosis, and surgical site infection) and 12-month mortality rate were recorded.Results:All the patients were followed up for 12-36 months [(18.0±5.1)months]. The operation duration and intraoperative blood loss were (68.2±8.4)minutes and (286.6±63.7)ml in the fracture line approach group, which were significantly shorter or less than (72.4±6.7)minutes and (321.3±76.2)ml in the modified Harding approach group ( P<0.05). However, there were no statistically significant differences in the incision length, blood transfusion volume or weight-bearing time between the two groups ( P>0.05). Harris hip scores and VAS scores at 1 month, 3 months, and at the last follow-up showed no significant differences between the two groups ( P>0.05). The dislocation rate was 0 in the fracture line approach group, superior to 13% in the modified Harding approach group ( P<0.05). There were no statistically significant differences in the fracture nonunion rate, incidence of other complications, or 12-month mortality rate between the two groups ( P>0.05). Conclusion:Compared with the modified Harding approach, hip hemiarthroplasty via the fracture line approach in the treatment of unstable intertrochanteric fractures in the elderly can shorten the operation time, reduce intraoperative blood loss, and lower the postoperative dislocation rate.

Objective:To investigate the clinical efficacy of 3D-printed metal augment or integrated acetabular prostheses for reconstruction of bone defects in hip revision.Methods:A total of 11 patients who underwent total hip revision in Zhengzhou Orthopaedic Hospital from June 2021 to July 2023 were retrospectively analysed. There were 5 males and 6 females, age 64.8±10.7 years (range, 58-75 years), and body mass index 23.3±4.8 kg/m 2 (range, 21-27 kg/m 2). Paprosky classification of acetabular bone defects: 3 cases of type IIA, 4 cases of type IIB, 3 cases of type IIIA, 1 case of type IIIB. Reasons for revision: 8 cases of aseptic loosening, 3 cases after infection exclusion procedure. A 3D-printed metal augment was used in 9 cases (8 cases of aseptic loosening and 1 case of infected exclusion procedure) and a 3D-printed integrated acetabulum was used in 2 cases (infected exclusion procedure). The time from primary total hip arthroplasty to revision was 11.8±5.6 years (range, 5-17 years). Harris hip score and visual analogue scale (VAS) were used to evaluate the improvement of hip function and pain recovery. The leg length discrepancy, vertical height and horizontal position of the hip rotation center were measured on pelvic anteroposterior X-ray films. Results:All patients successfully completed the operation. The operation time was 145.9±35.5 min (range, 110-159 min), and the intraoperative blood loss was 950.5±310.8 ml (range, 680-1,450 ml). The postoperative Harris hip function score was significantly higher than that before operation ( F=554.085, P<0.001). One year after operation, the Harris hip function score was 74.36±5.16, which was higher than that before operation 32.18±4.07, and the difference was statistically significant ( P<0.05). The VAS scores of all patients decreased after operation, and the difference was statistically significant compared with that before operation ( F=177.717, P<0.001). The VAS score at 1 year after operation was 1.27±0.65, which was lower than that before operation 6.18±1.17, and the difference was statistically significant ( P<0.05). The preoperative leg length discrepancy was 1.97±0.71 cm, which was greater than 0.69±0.52 cm at the last follow-up, and the difference was statistically significant ( t=4.824, P<0.001). The vertical height of the hip rotation center was 1.88±0.46 cm on the affected side and 1.67±0.35 cm on the healthy side, showing no significant difference ( t=1.205, P=0.242). The postoperative horizontal position of the hip rotation center was 3.48±0.55 cm on the affected side and 3.54±0.32 cm on the healthy side, and the difference was no statistically significant ( t=-0.313, P=0.758). One case had an intraoperative greater trochanteric fracture that healed 3 months after reduction and internal fixation. All patients were followed up for 21.3±9.5 months (range, 15-31 months). All incisions healed in one stage, and all patients were fully weight-bearing at 3 months after operation. At the last follow-up, there was no case of loosening, dislocation or infection of the prosthesis; 4 cases had mild claudication, 1 case had heterotopic ossification, and the patients had good hip flexion and extension functions, which did not affect daily life without further treatment. Conclusion:The clinical efficacy of 3D-printed metal augment or integrated acetabular prosthesis for reconstruction of acetabular bone defects is satisfactory, which can restore the normal center of rotation of the hip joint and has a low incidence of postoperative complications.

Objective:To compare the efficacy of hip hemiarthroplasty via the fracture line approach versus modified Harding approach in the treatment of unstable intertrochanteric fractures in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 79 elderly patients with unstable intertrochanteric fractures who were admitted to Zhengzhou Orthopaedic Hospital between July 2018 and February 2024, including 17 males and 62 females, aged 80-96 years [(84.0±9.6)years]. According to the AO classification, the fractures were classified as type A2 in 61 patients and type A3 in 18. All the patients underwent hip hemiarthroplasty, 33 of whom were treated via the fracture line approach (fracture line approach group) and 46 via the modified Harding approach (modified Harding approach group). The incision length, operation duration, intraoperative blood loss, blood transfusion volume, and weight-bearing time were documented. At 1 month, 3 months after surgery and at the last follow-up, hip function and pain were assessed using the Harris hip score and visual analogue scale (VAS). Postoperative dislocation rate, fracture nonunion rate, incidence of other complications (vascular injury, neurologic impairment, prosthesis loosening, lower extremity venous thrombosis, and surgical site infection) and 12-month mortality rate were recorded.Results:All the patients were followed up for 12-36 months [(18.0±5.1)months]. The operation duration and intraoperative blood loss were (68.2±8.4)minutes and (286.6±63.7)ml in the fracture line approach group, which were significantly shorter or less than (72.4±6.7)minutes and (321.3±76.2)ml in the modified Harding approach group ( P<0.05). However, there were no statistically significant differences in the incision length, blood transfusion volume or weight-bearing time between the two groups ( P>0.05). Harris hip scores and VAS scores at 1 month, 3 months, and at the last follow-up showed no significant differences between the two groups ( P>0.05). The dislocation rate was 0 in the fracture line approach group, superior to 13% in the modified Harding approach group ( P<0.05). There were no statistically significant differences in the fracture nonunion rate, incidence of other complications, or 12-month mortality rate between the two groups ( P>0.05). Conclusion:Compared with the modified Harding approach, hip hemiarthroplasty via the fracture line approach in the treatment of unstable intertrochanteric fractures in the elderly can shorten the operation time, reduce intraoperative blood loss, and lower the postoperative dislocation rate.

In the traditional theoretical system of traditional Chinese medicine， latent pathogenic factors deeply hiding in the liver and gallbladder of the Jueyin meridian are the core pathogenesis of chronic hepatitis B. Interferon can regulate immunity and eliminate viruses， and clinical cure can be achieved by penetrating and removing pathogenic factors and toxins. However， it often causes dizziness and confusion reactions in the initial stage of treatment， and long-term use can damage Qi-blood； furthermore， its therapeutic effect depends on the patient’s own vital Qi. When traditional Chinese medicine is used in combination with interferon， drug compatibility should be adjusted according to the dynamic changes of pathogenesis， which can reduce adverse reactions， enhance the therapeutic outcome， expand the applicable population of interferon， and improve the clinical symptoms of patients.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Objective To express nucleoprotein(NP) of influenza A virus in Bac-to-Bac TOPO system and evaluate its immunogenicity,so as to lay a foundation for the research of influenza virus NP protein vaccine.Methods The NP gene of influenza A H1N1(A/Guangdong-Maonan/SWL1536/2019_CNIC-1909) was amplified by PCR and connected to the vector pFastBac~(TM)/CT-TOPO~(TM),which was transformed into competent E.coli One Shot~(TM) Mach1~(TM) T1~R to prepare donor plasmid,and identified by PCR and sequencing.The donor plasmid was transformed into competent E.coli MAX Efficiency~(TM) DH10Bac~(TM),the positive monoclone was screened by blue-white spot screening,and the recombinant bacmid was extracted and identified by PCR.The recombinant bacmid was transfected into Sf9 insect cells to prepare the recombinant baculovirus,and the virus titer was detected by flow cytometry.After multiple rounds of amplification,the recombinant baculovirus infected Sf9 insect cells for the expression of the target protein NP,and the recombinant protein was purified by nickel ion affinity chromatography.Female BALB/c mice were subcutaneously inoculated with recombinant NP protein and PBS respectively,with six mice in each group.The serum specific antibody levels of mice were detected by ELISA,the IFN-γ secreted by spleen cells were detected by flow cytometry,and the CD4~+ and CD8~+ lymphocytes produced by spleen cells were detected by ELISpot.Two weeks after the last immunization,the mice were challenged with A/Guangdong Maonan/SWL 1536/2019_CNIC-1909 influenza virus through nasal cavity,and the body mass changes and survival rate of mice within 14 days after challenge were monitored.Results The results of PCR and sequencing showed that the donor plasmid was constructed correctly.PCR identification results confirmed that the recombinant bacmid was successfully constructed.The titer of recombinant baculovirus was 2.875 × 10~8ivp/mL.The recombinant NP protein showed specific binding to mouse anti-influenza A virus NP monoclonal antibody,with the purity of 91.3% after purification.Two weeks after the last immunization,compared with the PBS group,the serum specific antibody titer(t=0.288,P <0.000 1),the average number of IFNγ spots produced by spleen cells(t=9.235,P <0.000 1),and the number of CD4~+ and CD8~+T lymphocytes produced(t=10.870 and 6.200,P=0.008 4and 0.025 0,respectively) in mice of NA group increased significantly.The mice in PBS group all died within 5 days after infection,while in NP group,one mouse died 5 days after infection,and the other five mice survived.Conclusion The NP protein of influenza A virus expressed by Bac-to-Bac TOPO system has high immunogenicity and can produce strong humoral and cellular immune responses,which can provide certain protection for mice against influenza virus infection.

Objective:To investigate the clinical efficacy of 3D-printed metal augment or integrated acetabular prostheses for reconstruction of bone defects in hip revision.Methods:A total of 11 patients who underwent total hip revision in Zhengzhou Orthopaedic Hospital from June 2021 to July 2023 were retrospectively analysed. There were 5 males and 6 females, age 64.8±10.7 years (range, 58-75 years), and body mass index 23.3±4.8 kg/m 2 (range, 21-27 kg/m 2). Paprosky classification of acetabular bone defects: 3 cases of type IIA, 4 cases of type IIB, 3 cases of type IIIA, 1 case of type IIIB. Reasons for revision: 8 cases of aseptic loosening, 3 cases after infection exclusion procedure. A 3D-printed metal augment was used in 9 cases (8 cases of aseptic loosening and 1 case of infected exclusion procedure) and a 3D-printed integrated acetabulum was used in 2 cases (infected exclusion procedure). The time from primary total hip arthroplasty to revision was 11.8±5.6 years (range, 5-17 years). Harris hip score and visual analogue scale (VAS) were used to evaluate the improvement of hip function and pain recovery. The leg length discrepancy, vertical height and horizontal position of the hip rotation center were measured on pelvic anteroposterior X-ray films. Results:All patients successfully completed the operation. The operation time was 145.9±35.5 min (range, 110-159 min), and the intraoperative blood loss was 950.5±310.8 ml (range, 680-1,450 ml). The postoperative Harris hip function score was significantly higher than that before operation ( F=554.085, P<0.001). One year after operation, the Harris hip function score was 74.36±5.16, which was higher than that before operation 32.18±4.07, and the difference was statistically significant ( P<0.05). The VAS scores of all patients decreased after operation, and the difference was statistically significant compared with that before operation ( F=177.717, P<0.001). The VAS score at 1 year after operation was 1.27±0.65, which was lower than that before operation 6.18±1.17, and the difference was statistically significant ( P<0.05). The preoperative leg length discrepancy was 1.97±0.71 cm, which was greater than 0.69±0.52 cm at the last follow-up, and the difference was statistically significant ( t=4.824, P<0.001). The vertical height of the hip rotation center was 1.88±0.46 cm on the affected side and 1.67±0.35 cm on the healthy side, showing no significant difference ( t=1.205, P=0.242). The postoperative horizontal position of the hip rotation center was 3.48±0.55 cm on the affected side and 3.54±0.32 cm on the healthy side, and the difference was no statistically significant ( t=-0.313, P=0.758). One case had an intraoperative greater trochanteric fracture that healed 3 months after reduction and internal fixation. All patients were followed up for 21.3±9.5 months (range, 15-31 months). All incisions healed in one stage, and all patients were fully weight-bearing at 3 months after operation. At the last follow-up, there was no case of loosening, dislocation or infection of the prosthesis; 4 cases had mild claudication, 1 case had heterotopic ossification, and the patients had good hip flexion and extension functions, which did not affect daily life without further treatment. Conclusion:The clinical efficacy of 3D-printed metal augment or integrated acetabular prosthesis for reconstruction of acetabular bone defects is satisfactory, which can restore the normal center of rotation of the hip joint and has a low incidence of postoperative complications.

Acute-on-chronic liver failure （ACLF） is an acute and critical illness with a high short-term mortality rate， and current therapies mainly focus on elimination of causes， organ support， and prevention of complications. Although liver transplantation is the most effective treatment modality， its clinical application is limited， and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine， ACLF is classified into the same category as diseases such as “jaundice”， and unlike traditional jaundice which is mostly characterized by excess and heat syndromes， the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories， this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine， explores the evolution of ACLF syndromes， and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat， blood stasis-heat， and spleen deficiency， as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF， in order to provide ideas， methods， and evidence for the application of traditional Chinese medicine in ACLF.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*