Risk Factors and Dynamic Nomogram Development for Surgical Site Infection Following Open Wedge High Tibial Osteotomy for Varus Knee Osteoarthritis: A Retrospective Cohort Study.

Background: As the worldwide population ages, the population receiving open wedge high tibial osteotomy (OWHTO) is growing, and surgical site infection (SSI) is a rare but fatal surgical complication. This study aimed to identify risk factors independently associated with SSI following OWHTO and develop a predictive nomogram. Methods: Clinical data of patients who received OWHTO and followed up for more than 12 months in our hospital were retrospectively reviewed. Multivariable logistic regression was performed to determine independent risk factors for SSI and to construct predictive nomograms. The study further illustrated the predictive performance of the model by using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: A total of 1294 eligible patients were included in the study. Multivariate analysis revealed tobacco consumption (OR=3.44, p=0.010), osteotomy size ≥12 mm (OR=3.3, p=0.015), the use of allogeneic bone or artificial bone graft substitutes (allogeneic bone vs none, OR=4.08, p=0.037; artificial bone vs none, OR=5.16, p=0.047), Kellgren-Lawrence (K-L) grade IV (OR=2.5, p=0.046), systemic immune-inflammation index (SII) >423.62 (OR=6.2, p<0.001), high-sensitivity C-reactive protein (HCRP) >2.6 mg/L (OR=2.42, p=0.044), and a higher level of fasting blood glucose (FBG) (OR=1.32, p=0.022) were the independent predictors of SSI. The cutoff score of the model was 148, with a sensitivity of 76.0% and specificity of 81.0%. The concordance index (C-index) and Brier score of the nomogram were 0.856 and 0.017, and the corrected values after 1000 bootstrapping validations were 0.820 and 0.018, respectively. Furthermore, the ROC curve, calibration curve, and DCA exhibited excellent predictive accuracy and clinical applicability of the model. Conclusion: This study developed a dynamic nomogram based on seven predictors, which allowed surgeons to individualize risk stratification of patients and intervene promptly to reduce SSI rates.

Clinical therapeutic evaluation of vacuum sealing drainage and precise ultrasound-guided debridement in the treatment of non-lactational mastitis.

The aim of the present study was to compare the efficacy of vacuum sealing drainage (VSD) and precise ultrasound-guided debridement in the treatment of non-lactational mastitis and to determine the optimal surgical treatment. A set of 60 cases diagnosed with non-lactational mastitis who had received surgical treatment at the Department of Thoracic and Breast Surgery of Xiamen Hospital of Traditional Chinese Medicine (Xiamen, China) between July 2017 and June 2019 were included. According to the surgical method, 30 patients were assigned to the VSD group and 30 patients were assigned to the precise ultrasound-guided debridement group. The clinicopathological data of the two groups were compared. The overall rates of recurrence and new incidence were 6.8 and 8.5%, respectively. The mean total disease course was 5.3 months and all of the patients were cured after treatment. Except for the hospitalization time and postoperative pain scores, the clinicopathological data between the two groups were similar. The hospitalization time in the VSD group was significantly longer than that in the precise ultrasound-guided debridement group. Pain scores on the first and third days after the operation in the precise ultrasound-guided debridement group were significantly higher than those in the VSD group (P=0.008 and 0.001, respectively). In conclusion, the efficacies of VSD and precise ultrasound-guided debridement for the treatment of non-lactational mastitis were generally both satisfactory without significant differences. Of note, the former is suitable for patients with inverted nipples and obvious skin ulcerations, while the latter is mainly suitable for patients with abscesses, small surgical incisions and those who require short hospital stays.

Scopoletin Activates Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling Pathway and Improves Functional Recovery after Spinal Cord Injury in Rats.

BACKGROUND: Scopoletin (SPT) is known to exert neuroprotective autophagy effect. However, the efficacy of SPT in the treatment of spinal cord injury (SCI) has yet not been explored. The investigation was intended to elucidate whether SPT can exert neuroprotective effect by triggering neuronal autophagy after SCI. The study was also directed to investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in the autophagy facilitated by SPT. MATERIALS AND METHODS: The SCI was developed in female Sprague-Dawley rats by damaging the T10 spinal level using an impounder impact. Three animals groups were investigated - Sham group, SCI group, and SCI + SPT group. The SCI + SPT group was administered with SPT (100 mg/kg) intraperitoneally. Basso, Beattie, and Bresnahan scores and angle of incline test revealed that SPT administration improved the movement of hind limbs after SCI induction. RESULTS: Results indicated that SPT imparted neuronal protection, alleviated neuronal apoptosis, and improved neuronal autophagy. SPT-induced autophagy was identified by increased Beclin-1 expression and LC3B-positive neuronal cells. Further investigations revealed that SPT triggers the pathway involving AMPK/mTOR signaling, thereby stimulating autophagy in SCI-induced rat model. CONCLUSION: The findings of the present investigation strongly advocate the beneficial effects of SPT in the treatment of the SCI. SPT ameliorates the AMPK/mTOR signaling-induced autophagy and thereby improves functional recovery in SCI-induced rats.

Fabricating polydopamine-coated MoSe2-wrapped hollow mesoporous silica nanoplatform for controlled drug release and chemo-photothermal therapy.

BACKGROUND: Integration of several types of therapeutic agents into one nanoplatform to enhance treatment efficacy is being more widely used for cancer therapy. METHODS: Herein, a biocompatible polydopamine (PDA)-coated MoSe2-wrapped doxorubicin (DOX)-loaded hollow mesoporous silica nanoparticles (HMSNs) nanoplatform (PM@HMSNs-DOX) was fabricated for dual-sensitive drug release and chemo-photothermal therapy for enhancing the therapeutic effects on breast cancer. The HMSNs were obtained by a "structural difference-based selective etching" strategy and served as the drug carrier, exhibiting a high DOX loading capacity of 427 mg/g HMSNs-NH2, and then wrapped with PDA-coated MoSe2 layer to form PM@HMSNs-DOX. Various techniques proved the successful fabrication of the nanocomposites. RESULTS: The formed PM@HMSNs-DOX nanocomposites exhibited good biocompatibility, good stability, and super-additive photothermal conversion efficiency due to the cooperation of MoSe2 and PDA. Simultaneously, the pH/near-infrared-responsive drug release profile was observed, which could enhance the synergistic therapeutic anticancer effect. The antitumor effects of PM@HMSNs-DOX were evaluated both in vitro and in vivo, demonstrating that the synergistic therapeutic efficacy was significantly superior to any monotherapy. Also, in vivo pharmacokinetics studies showed that PM@HMSNs-DOX had a much longer circulation time than free DOX. In addition, in vitro and in vivo toxicity studies certified that PM@HMSNs are suitable as biocompatible agents. CONCLUSION: Our nanoplatform loaded with DOX displays pH/near-infrared-induced chemotherapy and excellent photothermal therapy, which hold great potential for cancer treatment.

Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to investigate the biological effects of extract from AM on breast cancer cell and its mechanism. METHODS: To prepare the extract, dried AM were ground and extracted with water extraction-ethanol supernatant method. Then the main isoflavones in the extract was detect by HPLC analysis. Furthermore, the anti-proliferative activity of AM extract was examined by MTT assay and morphological observation. Cell apoptosis was evaluated with flow cytometric analysis. The expressions of total and phosphorylated PI3K, GS3Kß, Akt and mTOR were determined by western blot analysis. RESULTS: HPLC analysis demonstrated that AM extract contained with four kinds of isoflavones, campanulin, ononin, calycosin and formononetin. The MTT test and morphological observation indicated that cells proliferation of MCF-7, SK-BR-3 and MDA-MB-231were inhibited by AM extract in a dose dependent manner. Furthermore, flow cytometric analysis displayed that after treated with 25 µg/ml and 50 µg/ml AM extract, apoptosis of breast cancer cells was significantly increased as compared with DMSO and blank control group (all p < 0.05). Western blot analysis found that the level of p-PI3K, p-GS3Kß, p-Akt, and p-mTOR were significantly decreased, but the level of total-mTOR was observably increased as compared with DMSO control group. CONCLUSIONS: Taken together, the inhibited cell proliferation and induced cell apoptosis effect of AM extract via PI3K/AKT/mTOR pathway confirmed the anti-tumor potential of AM. Therefore, our findings provide a new insight into anti-cancer effect of AM extract as a promising agent in breast cancer treatment.

Yiqi formula enhances the antitumor effects of erlotinib for treatment of triple-negative breast cancer xenografts.

Yiqi formula (YF), a traditional herbal prescription, has long been used to treat triple-negative breast cancer (TNBC) patients. The present study aims to investigate the effects and the related mechanism of YF for treatment of TNBC xenografts. MDA-MB-231 (human TNBC) cells were subcutaneously injected into the second mammary fat pad of 40 female nude mice, which were divided into four groups: control, erlotinib (an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor), YF, and combination (YF plus erlotinib). All treatments were administered orally for 30 days. Inhibition rate of tumor weight by erlotinib, YF, and the combination was 26.47%, 17.24%, and 39.15%, respectively. Western blotting showed that YF, erlotinib, and the combination downregulated p-EGFR (P < 0.01) and p-Akt1 (pT308) (P < 0.05) and upregulated PTEN compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). Similar results were detected by immunohistochemistry. Real-time quantitative PCR showed that YF, erlotinib, and the combination increased PTEN mRNA (P < 0.05, P < 0.01) compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). In conclusion, YF can regulate the main components of the PI3K/Akt pathway in TNBC xenografts. When YF was used in combination with erlotinib, it enhanced the antitumor effects of erlotinib on TNBC xenografts. These findings suggest that YF is suitable to use for the treatment of TNBC patients.

[Expression and significance of hypoxia-inducible factor-1α in patients with chronic obstructive pulmonary disease and smokers with normal lung function].

OBJECTIVE: To study the expression of hypoxia-inducible factor (HIF)-1α in lung tissues and sera from chronic obstructive pulmonary disease (COPD) patients and smokers with normal lung function and explore its clinical significance. METHODS: Lung tissue samples were obtained from 32 patients undergoing surgery for peripheral lung tumors. Lung function test was performed before lung cancer surgery. Based on lung function and smoking status, 32 patients were devided into three groups: smokers with stable COPD (COPD group, n=10), smokers with normal lung function (S group, n=10) and nonsmokers with nomal lung function (NS group, n=10). The preoperative fasting sera and lung tissues as far as possible away from the tumor site from all patients were collected. HIF-1α levels in sera and lung tissue homogenates were evaluated by ELISA. The expression of HIF-1α in airway epithelium, alveolar wall and blood vessel wall were detected by immunohistochemistry. Furthermore, the correlation between HIF-1α expression levels and pulmonary function was analyzed. RESULTS: Serum HIF-1α levels were significantly elevated in COPD group [(73.25 ± 6.12) pg/mL] and S group [(60.30 ± 8.00) pg/mL] as compared with NS group [(47.03 ± 8.43) pg/mL, P<0.01], and COPD group was significantly higher than S group (P<0.01). The concentrations of HIF-1α in lung tissue homogenates significantly increased in COPD group [(2.04 ± 0.24) pg/µg] and S group [(1.67 ± 0.34) pg/µg] as compared with NS group [(1.12 ± 0.33) pg/µg, P<0.01], and COPD group was also significantly higher than S group (P<0.01). HIF-1α expression was located in inflammatory cells and macrophages of airway epithelium, alveolar wall and small pulmonary artery wall. HIF-1α levels in sera and lung tissue homogenates showed negative correlations with FEV1/FVC and FEV1% predicted. CONCLUSION: HIF-1α levels are raised in sera and lung tissues of COPD patients and smokers with normal lung function, and they were positively correlated with the severity of airflow limitation.

[Expression and significance of immunoglobulin free light chains in serum and lung tissues from patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the association of free immunoglobulin light chain (FLC) with clinical manifestations and lung inflammation in smokers with normal lung function and chronic obstructive pulmonary disease (COPD) patients. METHODS: Thirty-two patients with peripheral lung cancer undergoing surgical resection were enrolled from the Department of Thoracic Surgery,Affiliated Hospital of Xuzhou Medical College. They were divided into non-smoking with normal lung function group (non-smoking group, 10 cases), smoking with normal lung function group (smoking group, 12 cases) and smoking with stable COPD group (COPD group, 10 cases). Their preoperative fasting serum and lung tissues away from cancer were used in the study.Enzyme-linked immunesorbent assays (ELISA) were used to detect the levels of FLC-λ and FLC-κ in serum and lung tissue homogenates. The expression of FLC-λ and FLC-κ in the airway epithelium, alveolar wall and blood vessel wall was detected by immunohistochemistry. The correlation between FLC levels and pulmonary functions were analyzed. RESULTS: The serum levels of FLC-λ and FLC-κ in COPD group and smoking group were (35 ± 11),(38 ± 12) and (26 ± 9),(26 ± 8) mg/L, respectively. They were all significantly increased compared with the non-smoking group [(16 ± 7),(16 ± 5) mg/L]. The differences were all statistically significant (q = 3.590-7.482, P < 0.01), and those of the COPD group were significantly higher than those of the smoking group (q = 3.209-4.198, P < 0.05 and P < 0.01). The concentrations of FLC-λ and FLC-κ in lung tissue homogenates of the COPD group and the smoking group were (1.29 ± 0.31),(1.32 ± 0.30) and (0.86 ± 0.42),(0.85 ± 0.37) µg/mg, respectively. They were all significantly increased compared with those of the non-smoking group [(0.45 ± 0.18),(0.42 ± 0.13) µg/mg],(q = 4.178- 9.795, P < 0.05 and P < 0.01). The levels of FLC-λ and FLC-κ in the lung tissue homogenates from the COPD group were significantly higher than those from the smoking group (q = 4.269-4.349, all P < 0.05). The expression of FLC-λ and FLC-κ was detected in airway epithelium, alveolar wall and blood vessel wall. The levels of FLC-λ and FLC-κ in serum and lung tissue homogenates showed a negative correlation with FEV1 percentage of predicted value (r = -0.476 to -0.591, all P < 0.01). CONCLUSIONS: Expressions of FLC were increased in the serum and the lung tissues of COPD patients and smokers with normal lung function, and closely correlated with airflow limitation. The results suggest that FLC plays a proinflammatory role in the pathogenesis of COPD.

[Effects of Astragalus polysaccharide on proliferation and Akt phosphorylation of the basal-like breast cancer cell line].

OBJECTIVE: To investigate the effects of Astragalus polysaccharide (APS) on proliferation of basal-like breast cancer cell line MDA-MB-468 cells and Akt phosphorylation in MDA-MB-468 cells. METHODS: APS at different concentrations was used to culture MDA-MB-468 cells for different time periods, and then proliferation of MDA-MB-468 cells was assayed using methyl thiazolyl tetrazolium (MTT) assay to determine the time- and dose-dependent effects of APS. For observing the effects of APS on phosphor-Akt (p-Akt), in-cell Western blot method was used after 1, 2, 4 and 7 d of culture in APS to detect protein expressions of p-Akt (Thr308) and p-Akt (Ser473). Protein levels of the key targets in p53/murine double minute 2 (MDM2) signaling pathway, such as p53, MDM2 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were also detected. After PTEN gene was silenced by small interfering RNA (siRNA) in MDA-MB-468 cells, expressions of p-Akt (Thr308 and Ser473) were assayed by the in-cell Western blot method after 2 d of APS treatment. RESULTS: APS at 1 and 0.5 mg/mL concentrations effectively inhibited the proliferation of MDA-MB-468 cells and was used in subsequent tests. Compared with the control group, APS decreased the protein expression of p-Akt (Thr308) in MDA-MB-468 cells after 1-, 2-, 4- and 7-day culture, and also decreased the protein expression of p-Akt (Ser473) and up-regulated the protein expression of MDM2 in MDA-MB-468 cells after 1- and 2-day culture. Expressions of p53 and PTEN were up-regulated after 7 d of APS culture. After silencing PTEN gene by siRNA, APS could not mediate Akt phosphorylation. CONCLUSION: APS can inhibit proliferation of basal-like breast cancer cell line MDA-MB-468, and down-regulate the expression of Akt phosphorylation. The antiproliferation mechanisms may be related to its effects of up-regulating the expressions of p53 and PTEN by regulating p53/MDM2 positive and negative feedback loops.