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 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.

Purpose: Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy,which is associated with the progression of carcinoma. Yet, it is still unclear whetherLC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aimto explore the predictive value of LC3B on prognosis of ICC, and to establish a novel andavailable nomogram to predict relapse-free survival (RFS) and overall survival (OS) for thesepatients after curative-intent hepatectomy. Materials and Methods: From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the ThirdAffiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolledpatients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry. Results: The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariateCox regression analysis, independent risk factors for 5-year OS were cancer antigen 125,microvascular invasion, LC3B expression and lymph node metastasis. Except for the above4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factorsfor 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and0.747, respectively. Conclusion The nomograms based on LC3B can be considered as effective models to predict postoperativesurvival for ICC patients.

Objective To discuss the treatment of periprosthetic femoral fractures (PFF) with unstable prosthesis by replacement of long-stem femoral prosthesis and internal fixation.Methods From December 2005 to December 2014,15 PFF patients with unstable prosthesis (15 hips) following were treated at our department.They were 10 men and 5 women,aged from 64 to 89 years (mean,76.2 years).Their primary surgeries included total hip arthroplasty in 13 cases and biological bi-polar replacement of femoral head in 2.Two prostheses were cement and 13 biological.By Vancouver classification,9 cases were type B2,and 6 type B3.The unstable prostheses in the 15 cases were replaced by long-stem femoral ones,followed by internal fixation.At the last follow-ups,clinical outcome were evaluated by Harris scoring and images of PFF by Beals & Tower criteria.Complications were documented.Results One died 4 months after operation.The other 14 patients were followed up for an average of 4.5 years (from 6 months to 9 years).Fracture union was achieved in 12 cases after an average of 3.9 months (from 3 to 9 months).Nonunion occurred in 2 cases.Imaging evaluation revealed 9 excellent cases,3 good ones and 2 poor ones.The Harris scores at the last follow-up averaged was 82.3 points (from 50 to 100 points).Deep vein thrombosis occurred preoperatively in one case and posterior tibial vein thrombosis occurred in 2 cases respectively on day 3 and day 10 postoperatively.No such complications occurred as malunion,fixation failure,dislocation or prosthesis loosening.Conclusion Satisfactory outcomes can be achieved by replacement of long-stem femoral prosthesis combined with appropriate fixation for treatment of PFF with unstabrosthesis.

BACKGROUNDImplanted medical catheter-related infections are increasing, hence a need for developing catheter polymers bonded to antimicrobials. We evaluated preventive effects of levofloxacin-impregnated catheters in catheter-related Psuedomonas aeruginosa (strain PAO1) infection.

METHODSDrug release from levofloxacin-impregnated catheters was measured in vitro. Levofloxacin-impregnated catheters and polyvinyl chloride (PVC) catheters were immersed in 5 ml 50% Luria Bertani medium containing 10(8) CFU/ml Pseudomonas aeruginosa then incubated for 6, 12, 24 or 48 hours at 37°C when bacteria adhering to the catheters and bacteria in the growth culture medium were determined. Impregnated and PVC catheters were singly implanted subcutaneously in mice, 50 µl (10(7)CFU) of PAO1 was injected into catheters. After the first and fifth days challenge, bacterial counts on implanted catheters and in surrounding tissues were determined microbiologically. Bacterial colonization and biofilm formation on implanted catheters were assessed by scanning electron microscopy.

RESULTSDrug release from levofloxacin-impregnated catheters was rapid. Levofloxacin-impregnated catheters had significantly fewer bacteria compared to PVC in vitro. After first and fifth day of challenge, no or significantly fewer bacteria adhered to impregnated catheters or in surrounding tissues compared to PVC. Scanning electron microscopical images after first day displayed from none to significantly fewer bacteria adhering to impregnated implanted catheters, compared to bacteria and microcolonies adhering to PVC catheters. After the fifth day, no bacteria were found on impregnated catheters, compared to clusters surrounding mucus-like substance and coral-shaped biofilms with polymorphonuclear leukocyte on PVC catheters. After the first day of challenge, secretion occurred in all implanted catheters with surrounding tissues mildly hyperaemic and swollen. After the fifth day, minute secretions inside impregnated catheters and no inflammation in tissues, whereas purulent secretion inside PVC catheters and abscesses in surrounding tissues.

CONCLUSIONLevofloxacin-impregnated catheter is a promising new strategy for prevention of catheter-related Psuedomonas aeruginosa infection.

Animals ; Biofilms ; drug effects ; Catheters, Indwelling ; microbiology ; Female ; Levofloxacin ; therapeutic use ; Mice ; Pseudomonas Infections ; prevention & control ; Pseudomonas aeruginosa ; pathogenicity

Objective To investigate the risk factors and treatment efficiency for lung cancer patients with venous thromboembolism (VTE). Methods Total 282 cases of lung cancer patients with VTE were enrolled into two groups , including the VTE group and the non-VTE group , for comparation analysis based on a series of clinical data. Results The occupation rate of adenocarcinoma and Ⅳ period were 65.28% and 87.50% in VTE group, respectively, higher than those of 51.43% and 75.71% in the non-VTE group. The increased rate of blood viscosity and d-dimer respectively were 65.28% and 70.83%, higher than those of 51.43% and 56.67% in the non-VTE group, with significant differences (P < 0.05, respectively). Result of logistic regression analysis showed that tumor stage , d-dimer levels , smoking , age , and blood viscosity levels were highly correlated with venous thrombosis in patients with lung cancer, and the OR value among them was 3.802, 2.339, 5.814, 3.875 and 6.404, respectively, with significant differencees (P < 0.05, respectively). Conclusions Lung adenocarcinoma with stage Ⅳ, smoking , age and increase of blood viscosity and d-dimer were the important risk factors for VTE in patients with lung cancer chemotherapy. Timely assessment of risk factors and early anticoagulation therapy in lung cancer patients with venous thromboembolism associated with VTE can improve the treatment efficacy and reduce the complications.

Objective To reduce the animal component contamination for human embryonic stem cells ( hESCs ) and to simplify hESCs culture process , we develop a new coating substrate which can support the hESCs growth without dif -ferentiation, and is easy to store and use. Methods Mouse embryonic fibroblasts(MEF)were fixed on the surface of plate by methanol.hESCs were cultured on this new substrate and were passaged every 5 to 6 days.After 10 passages, we checked the cell morphology , alkaline phosphatase expression , embryonic specific markers and the differentiation ability in vitro.Results After 10 passages , the hESCs grew well on this new substrate and maintained the typical hESCs morpholo -gy.Alkaline phosphatase staining was positive .Immunofluorescence staining showed that the expressions of Oct 4, SSEA4, Tra-1-60 were positive .The cells formed embryoid body in vitro .Conclusions This methanol-fixed MEF substrate can support the growth of undifferentiated hESCs .The coating material can be produced in large scale and stored for a long time.It provides a new and relatively easy way to amplify hESCs .

Objective To investigate the effect of pentazocine combined with midazolam on intubation stress response in slow induction of anesthesia. Mtheods Forty ASAⅠ~Ⅱpatients were divided into two groups. Anesthesia was induced with midazolam 0.03 mg/kg in both groups,and pentazocine 0.8 mg/kg (i.v.) was given in pentazocine group or fentanyl 2 μg/kg (i.v.) in fentanyl group. Five minutes later, 2 mL of 1% decicaine was administered by cricothyroid membrane puncture to facilitate the intubation.The SpO2, circulatory indexes (HR, SBP, DBP, BIS) and sedation level were measured at T0, T1, T2, T3, T4, T5, T6. Results Both pentazocine and fentanyl can inhibit stress responses to tracheal intubation effectively,but pentazocine group is better than fentanyl group on the cardiovascular stability during slow induction of anesthesia. Conclusion Pentazocine 0.8 mg/kg can inhibit stress responses to tracheal intubation effectively with a low incidence of adverse reactions in the slow induction of anesthesia.