PINK1-mediated mitophagy contributes to glucocorticoid-induced cathepsin K production in osteocytes.

Background: Glucocorticoid (GC) is one of frequently used anti-inflammatory agents, but its administration is unfortunately accompanied with bone loss. Although sporadic studies indicated that osteocytes are subject to a series of pathological changes under GC stress, including overexpression of cathepsin K, the definite role of osteocytes in GC-induced bone loss remains largely unclear. Methods: Gene expression of Ctsk and protein levels of cathepsin K were assessed in MLO-Y4 cell lines exposed to dexamethasone (Dex) of different time (0, 12, 24 hours) and dose (0, 10-8 and 10-6 M) courses by RT-qPCR and western blotting, respectively. Confocal imaging and immunostaining were then performed to evaluate the effects of osteocyte-derived cathepsin K on type I collagen in a primary osteocyte ex vivo culture system. MitoTracker Red was used to stain mitochondria for mitochondria morphology assessment and JC-1 assay was employed to evaluate the mitochondria membrane potential in MLO-Y4 cells following Dex treatment. Activation of PINK1-mediated mitophagy was evaluated by immunostaining of the PINK1 protein and CytoID assay. Mdivi-1 was used to inhibit mitophagy and siRNAs were used for the inhibition of Pink1 and Atg5. Results: GC triggered osteocytes to produce excessive cathepsin K which in turn led to the degradation of type I collagen in the extracellular matrix in a primary osteocyte ex vivo culture system. Meanwhile, GC administration increased mitochondrial fission and membrane depolarization in osteocytes. Further, the activation of PINK1-mediated mitophagy was demonstrated to be responsible for the diminishment of dysfunctional mitochondria in osteocytes. Examination of relationship between mitophagy and cathepsin K production revealed that inhibition of mitophagy via knocking down Pink1 gene abolished the GC-triggered cathepsin K production. Interestingly, GC's activation effect towards cathepsin K via mitophagy was found to be independent on the canonical autophagy as this effect was not impeded when inhibiting the canonical autophagy via Atg5 suppression. Conclusion: GC-induced PINK1-mediated mitophagy substantially modulates the production of cathepsin K in osteocytes, which could be an underlying mechanism by which osteocytes contribute to the extracellular matrix degradation during bone loss. The Translational potential of this article: Findings of the current study indicate a possible role of osteocyte mitophagy in GC-induced bone loss, which provides a potential therapeutic approach to alleviate GC-induced osteoporosis by targeting PINK1-mediated osteocytic mitophagy.

Application of curved ablation in liver cancer with special morphology or location: Report of two cases.

BACKGROUND: Liver cancer is one of the most common malignant tumors with a high incidence and mortality. Hepatitis-liver cirrhosis-liver cancer is known as the trilogy of liver cancer. At present, due to significant development of imaging interventions, they occupy an irreplaceable position in the field of liver cancer treatment, especially ultrasound-guided ablation. Because patients with liver cancer often present with liver cirrhosis, which leads to morphological deformation of the liver, it is difficult to perform a linear ablation of liver cancer in the areas near the phrenic top and within large blood vessels, among others. The present study reports on two cases of liver cancer that have been subjected to curvilinear ablation. After 1 mo, magnetic resonance imaging showed complete ablation, demonstrating that ultrasound-guided curved ablation is feasible and effective in the treatment of liver cancer. CASE SUMMARY: Two patients were treated at the Liver Disease Department of the Xixi Hospital Affiliated to Zhejiang University of Chinese Medicine in 2019. Because the first liver cancer patient's tumor was located close to the diaphragm, it was difficult to complete a straight needle ablation procedure in one session. In order to achieve accurate and minimally invasive treatment of this tumor, a curved needle ablation procedure was designed. The second patient presented with a hepatic cyst in front of the tumor. In order not to damage the hepatic cyst, a looper needle ablation technique was used. The procedure was successfully completed in both cases. CONCLUSION: Curved ablation is a new technique that can be used to treat tumors situated in a variety of locations, providing new ideas for interventional techniques. Its operation difficulty is higher and further animal experiments are necessary to improve the operation procedure.

Retrospective study of the efficacy and toxicity of lobaplatin in combined chemotherapy for metastatic breast cancer.

OBJECTIVE: To study the efficacy and adverse reactions of lobaplatin combined with other chemotherapy drugs in the treatment of metastatic breast cancer. METHODS: This retrospective analysis enrolled 114 patients who were diagnosed with advanced breast cancer from January 2010 to December 2015. Lobaplatin and another chemotherapeutic agent were given to patients. The efficacy and side effects were evaluated after at least two cycles of chemotherapy. RESULTS: Therapeutic efficacy and adverse reactions could be evaluated in 112 patients with 2 complete response (CR) patients, 31 cases of partial response (PR), 52 cases of stable disease (SD) and 27 cases of progressive disease (PD). The overall response rate (ORR) was 29.5% and the disease control rate (DCR) was 75.9%. The median time to progression (TTP) was 7.7 months, and the median overall survival (OS) was expected to be 28.0 months. The main side effects were myelosuppression. Twenty five patients (21.9%) had grade 3/4 neutrophil suppression, 18 patients (15.8%) had grade 3/4 thrombocytopenia. Other toxicities included gastrointestinal reaction, peripheral neuropathy, stomatitis, hepatic dysfunction, fatigue and skin rashes, which were alleviated by symptomatic treatment. CONCLUSION: Lobaplatin-based regimen chemotherapy for advanced metastatic breast cancer patients is effective and well tolerated.

Down-regulation of CXCL11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition.

BACKGROUND: The poor prognosis of colorectal cancer (CRC) largely results from local invasion and tumor metastases. Epithelial-mesenchymal transition (EMT) is a key step in the progression of solid tumors and plays a vital role in tumor metastasis. Recent studies demonstrate that C-X-C motif chemokine 11 (CXCL11) is involved in various cancers' progression. However, its biological activity in CRC needs deeper exploration. METHODS: The level of CXCL11 in CRC tissues and cell lines was determined using the quantitative real-time PCR (qRT-PCR) assay. The MTT, colony formation, wound healing and Transwell invasion assays were applied to assess the role of CXCL11 in CRC cell growth, migration and invasion, in vitro, respectively. A xenograft model was constructed to analyze the function of CXCL11 in CRC cell growth in vivo. RESULTS: CXCL11 was over-expressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited CRC cell migration, invasion and EMT in vitro. In addition, down-regulation of CXCL11 reduced CRC cell growth and metastasis in vivo. Finally, we revealed that repression of CXCL11 inhibited the metastatic ability of CRC cell in a N-cadherin dependent manner. CONCLUSION: In summary, this study explicates the oncogenic activities of CXCL11 in CRC cell growth and metastasis.

Simplified Chinese version of hip and knee replacement expectations surveys in patients with osteoarthritis and ankylosing spondylitis: cross-cultural adaptation, validation and reliability.

BACKGROUND: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) and Knee Replacement Expectations Survey (HSS-TKRES) are widely used tools developed to assess patients' preoperative expectations for total hip and knee arthroplasty. This study aimed to translate and adapt the HSS-THRES and HSS-TKRES into Chinese versions (SC-THRES/TKRES) and evaluate their psychometric properties in patients with osteoarthritis (OA) and ankylosing spondylitis (AS). METHODS: Patients scheduled for total hip (104 hip OA and 51 AS) or knee replacements (101 knee OA) were recruited in this study. Confirmatory Factor Analysis (CFA) was used to evaluate structural validity. The internal consistency was assessed by the Cronbach's α coefficient. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The construct validity was analyzed by evaluating the correlations between SC-THRES/TKRES and the Expectation WOMAC. The correlations with the Expectation WOMAC were tested against our hypotheses. We additionally compared preoperative expectations of AS patients to those of hip OA patients. RESULTS: The results of CFA for the SC-THRES and SC-TKRES demonstrated good fit. The results for the SC-THRES/TKRES revealed good test-retest reliability and good internal consistency (AS: ICC = 0.893, Cronbach's α = 0.815; hip OA: ICC = 0.878, Cronbach's α = 0.814; knee OA: ICC = 0.806, Cronbach's α = 0.808). The correlations between the SC-THRES/TKRES and the Expectation WOMAC were moderate (0.541 for AS, 0.490 for hip OA and 0.465 for knee OA), which were consistent with the hypotheses. CONCLUSION: The SC-THRES/TKRES are reliable, valid for the evaluation of Chinese patients with OA and AS undergoing total hip and knee arthroplasty. The surveys can be used as part of preoperative assessments. Meanwhile, additional research is needed to replicate these findings and to assess the content validity in a larger sample.

Determinants of Calcium Infusion Rate During Continuous Veno-venous Hemofiltration with Regional Citrate Anticoagulation in Critically Ill Patients with Acute Kidney Injury.

BACKGROUND: It is unclear that how to decide the calcium infusion rate during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to assess the determinants of calcium infusion rate during CVVH with RCA in critically ill patients with acute kidney injury (AKI). METHODS: A total of 18 patients with AKI requiring CVVH were prospectively analyzed. Postdilution CVVH was performed with a fixed blood flow rate of 150 ml/min and a replacement fluid flow rate of 2000 ml/h for each new circuit. The infusion of 4% trisodium citrate was started at a rate of 29.9 mmol/h prefilter and adjusted according to postfilter ionized calcium. The infusion of 10% calcium gluconate was initiated at a rate of 5.5 mmol/h and adjusted according to systemic ionized calcium. The infusion rate of trisodium citrate and calcium gluconate as well as ultrafiltrate flow rate were recorded at 1, 2, 4, 6, 12, and 24 h after starting CVVH, respectively. The calcium loss rate by CVVH was also calculated. RESULTS: Fifty-seven sessions of CVVH were performed in 18 AKI patients. The citrate infusion rate, calcium loss rate by CVVH, and calcium infusion rate were 31.30 (interquartile range: 2.70), 4.60 ± 0.48, and 5.50 ± 0.35 mmol/h, respectively. The calcium infusion rate was significantly higher than that of calcium loss rate by CVVH (P < 0.01). The correlation coefficient between the calcium and citrate infusion rates, and calcium infusion and calcium loss rates by CVVH was -0.031 (P > 0.05) and 0.932 (P < 0.01), respectively. In addition, calcium infusion rate (mmol/h) = 1.77 + 0.8 × (calcium loss rate by CVVH, mmol/h). CONCLUSIONS: The calcium infusion rate correlates significantly with the calcium loss rate by CVVH but not with the citrate infusion rate in a fixed blood flow rate during CVVH with RCA.

Rapid screening of residual pesticides on fruits and vegetables using thermal desorption electrospray ionization mass spectrometry.

RATIONALE: Conventional mass spectrometry is encumbered by laborious and inconvenient sample pretreatment. Ambient thermal desorption electrospray ionization mass spectrometry (TD-ESI-MS) is most noted for its rapid, simple, and sensitive detection capabilities. In this study, TD-ESI-MS was used to rapidly characterize residual pesticides on the surfaces of fruits and vegetables. METHODS: A direct sampling probe was used to obtain analytes from sample surfaces. MS and MS/MS analyses were performed on fruits and vegetables via TD-ESI-MS. External calibration curves and reproducibility tests were performed using liquid pesticide standards. Pesticide decay and distribution on samples was studied, as well as the removal of residual pesticides via soaking in water or detergent baths. RESULTS: Since sample pretreatment was unnecessary, an analysis was completed in approximately 15 s or less, with no visible sample damage. Mass spectra were obtained for 22 pesticides. Linear calibrations (R(2) from 0.9414-0.999) had limits of detection as low as 0.5 µg·L(-1), with satisfactory reproducibilities for liquids and solids. Pesticides on sample surfaces decayed over 2 weeks under ambient conditions. Residual pesticides localized at the fruit peel. Detergent baths removed more pesticide than water baths. CONCLUSIONS: TD-ESI-MS was used to rapidly screen residual pesticides in liquids and solids. Pesticides were found on fruits and vegetables, where the decay, distribution, and removal of pesticides on samples were also explored. Due to short analysis times, the technique allows for high-throughput analyses for applications in food and environmental safety.

Rapid characterization of chemical compounds in liquid and solid states using thermal desorption electrospray ionization mass spectrometry.

Rapid characterization of thermally stable chemical compounds in solid or liquid states is achieved through thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS). A feature of this technique is that sampling, desorption, ionization, and mass spectrometric detection are four separate events with respect to time and location. A metal probe was used to sample analytes in their solid or liquid states. The probe was then inserted in a preheated oven to thermally desorb the analytes on the probe. The desorbed analytes were carried by a nitrogen gas stream into an ESI plume, where analyte ions were formed via interactions with charged solvent species generated in the ESI plume. The analyte ions were subsequently detected by a mass analyzer attached to the TD-ESI source. Quantification of acetaminophen in aqueous solutions using TD-ESI/MS was also performed in which a linear response for acetaminophen was obtained between 25 and 500 ppb (R(2) = 0.9978). The standard deviation for a reproducibility test for ten liquid samples was 9.6%. Since sample preparation for TD-ESI/MS is unnecessary, a typical analysis can be completed in less than 10 s. Analytes such as the active ingredients in over-the-counter drugs were rapidly characterized regardless of the different physical properties of said drugs, which included liquid eye drops, viscous cold syrup solution, ointment cream, and a drug tablet. This approach was also used to detect trace chemical compounds in illicit drugs and explosives, in which samples were obtained from the surfaces of a cell phone, piece of luggage made from hard plastic, business card, and wooden desk.

Phenolic acids analysis in ligusticum chuanxiong using HPLC.

A reversed-phase high-performance liquid chromatographic method with diode array UV detection is developed for the determination of five kinds of phenolic acids common in herbal medicines. Based on this method, ferulic acid and caffeic acid are found to be two main phenolic acids in Chuanxiong (one of the important crude drugs in traditional Chinese medicine). More important, ferulic acid is found to exist in free form, and caffeic acid--a previously unreported component--is found to exist in esterified or insoluble-bound form.

[Chronomodulated chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid for advanced gastric cancer].

OBJECTIVE: The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety. METHODS: Twenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles. RESULTS: Twenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2. CONCLUSION: Chronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.