OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

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 explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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 risk factors associated with one-year mortality following surgery for intertrochanteric fractures in elderly patients and develop a survival prediction model.Methods:A retrospective analysis was conducted on clinical data from 532 elderly patients with intertrochanteric fractures admitted to the People's Hospital of Xinjiang Uygur Autonomous Region and the People's Hospital of Xinyang between January 2020 and September 2022.Patient demographics, laboratory indicators, and surgical variables were documented.The primary outcome assessed was the one-year mortality rate.Risk factors were identified through univariate and multivariate Cox regression analyses, leading to the development of a prognostic model.The model's predictive performance was evaluated using the Concordance Index(C-Index), time-dependent receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).Results:Multivariate Cox regression analysis identified several key factors associated with one-year mortality after intertrochanteric fractures in elderly patients.These factors included the modified five-item frailty index( OR=1.338, 95% CI: 1.147-1.561, P<0.001), ICU admission( OR=1.694, 95% CI: 1.230-2.333, P=0.001), preoperative hemoglobin levels( OR=1.281, 95% CI: 1.016-1.616, P=0.036), surgical waiting time( OR=1.570, 95% CI: 1.063-2.319, P=0.023), and age( OR=2.196, 95% CI: 1.712-2.816, P<0.001).The prediction model showed good consistency with a C-Index of 0.769(95% CI: 0.723-0.818)in the modeling group and 0.715(95% CI: 0.612-0.750)in the validation group.Time-dependent ROC areas under the curve were 0.802(95% CI: 0.722-0.850)and 0.718(95% CI: 0.640-0.808)for the modeling and validation groups, respectively.Calibration curves for both groups indicated a good model fit, and decision curve analysis demonstrated a positive net benefit, highlighting the clinical applicability of the model. Conclusions:The modified five-item frailty index, ICU admission, preoperative hemoglobin, surgical waiting time, and age independently predict one-year mortality after surgery for intertrochanteric fractures in elderly patients.This prognostic model, utilizing these factors, shows high predictive accuracy, assisting clinicians in quick personalized assessments and setting informed expectations in clinical practice.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective:To investigate the effects of tranexamic acid on the drainage duration after primary unilateral total knee arthroplasty (TKA).Methods:From June 2017 to December 2018, a total of 182 patients (42 males and 140 females) who underwent primary TKA were included. The age of patients was 68.1±7.1 years (60-76 years). According to the random number table, the subjects were divided into four groups: 45 cases in tranexamic acid group 1 (TXA1), 46 cases in tranexamic acid group 2 (TXA2), 46 cases in tranexamic acid group 3 (TXA3) and others in none tranexamic acid group (NTXA). The patients in TXA1-3 groups received intravenous infusion combined with local application of tranexamic acid. The patients in NTXA group were locally perfused in the joint cavity with 100 ml normal saline after surgery. The drainage volume, total blood loss, invisible blood loss, degree of postoperative joint swelling, Hospital for Special Surgery (HSS) and visual analogue scale (VAS) of pain were compared among the four groups.Results:The postoperative drainage volume of TXA1-3 groups was 85.5±34.3 ml, 189.4±72.3 ml and 215.3±93.4 ml, respectively, which were less than that of the NTXA group (351.3±113.5 ml) with significant difference ( F=11.5, P=0.005). The postoperative drainage volume of TXA1 group was less than that of TXA2-3 groups. The total postoperative blood loss was 699.0±255.7 ml, 710.4±296.1 ml, and 715.8±248.2 ml in the TXA1-3 groups, respectively, which were less than that of the NTXA group (1 130.5±354.2 ml) with significant difference ( F=13.1, P=0.001). At the 4th day after TKA, the knee swelling degree of TXA1-3 groups was 1.25±0.07, 1.13±0.12, and 1.12±0.13, respectively, which were less severe than that of the NTXA group (1.43±0.22) with significant difference ( F=8.23, P=0.015). There were 2 cases with positive bacterial culture in NTXA group and TXA3, 3 cases with hematoma and 1 case with delayed wound healing in the NTXA group. Conclusion:The application of tranexamic acid after TKA can reduce postoperative drainage volume, latent blood loss and total blood loss. The removal of the drainage at 18 h after the operation can not only drain completely, relieve pain and promote knee joint function, but also effectively reduce the risk of infection associated drainage.