Inhibition of thioredoxin reductase and upregulation of apoptosis genes for effective anti-tumor sono-chemotherapy using a meso-organosilica nanomedicine.

The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity.

Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer-associated fibroblasts (CAFs) show multiple tumor-promoting effects and can induce tumor immune evasion and drug-resistance. Regulating CAFs can be a potential strategy to augment systemic anti-tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs' tumor-promoting and immune-suppressive phenotypes. Accordingly, a controllable and TME-responsive hydrogen therapy based on a CaCO3 nanoparticles-coated magnesium system (Mg-CaCO3) is developed. The hydrogen therapy by Mg-CaCO3 can not only directly kill tumor cells, but also inhibit pro-tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg-CaCO3 can significantly suppress tumor growth, turn the "cold" primary tumor into "hot", and stimulate systematic anti-tumor immunity, which is confirmed by the bilateral tumor transplantation models of "cold tumor" (4T1 cells) and "hot tumor" (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti-tumor immune stimulating strategy by remodeling tumor stromal microenvironment.

Integrated organosilica nanomedicine enables sonoimaging, sonochemistry and antitumor sonodynamic therapy.

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications.

Silencing Lnc-HES1-10 Inhibits Osteosarcoma Cells Proliferation, Invasive Ability, and Metastasis.

BACKGROUND: Long noncoding RNA (LncRNA) play a vital role in the development and pathophysiology of osteosarcoma (OS). However, the LncRNA activated by HES1-10 in OS has not been furthered investigated. This present study aims to show the possible function of Lnc-HES1-10 in OS. METHODS: Cell proliferation in vitro were assessed by the MTT assay, whereas the migration and invasion abilities of OS cell lines were measured by wound-healing migration assay and transwell invasion assay, respectively. Quantitative reverse transcriptase polymerase chain reaction and western blot analysis was used to detected the expression level of HES1-10. RESULTS: The present study demonstrated that the Lnc-HES1-10 is overexpressed in OS and associated with poor prognosis of patients. In addition, the results revealed that Lnc-HES1-10 is overexpressed in MG63 and 143B OS cell lines and promote proliferation on both cell lines in vitro. Furthermore, migration and invasion abilities of MG63 and 143B cells are suppressed after silencing Lnc-HES1-10. CONCLUSION: Our finding demonstrates that HES1-10 plays a crucial role in regulating OS growth and metastasis.

Bimetallic Organic Frameworks of High Piezovoltage for Sono-Piezo Dynamic Therapy.

Piezoelectric materials produce charges to directly act on cancer medium or promote the generation of reactive oxygen species (ROS) for novel tumor therapy triggered by sonography. Currently, piezoelectric sonosensitizers are mainly used to catalyze ROS generation by the band-tilting effect for sonodynamic therapy. However, it remains a challenge for piezoelectric sonosensitizers to produce high piezovoltages to overcome the bandgap barrier for direct charge generation. Herein, Mn-Ti bimetallic organic framework tetragonal nanosheets (MT-MOF TNS) are designed to produce high piezovoltages for novel sono-piezo (SP)-dynamic therapy (SPDT) with remarkable antitumor efficacy in vitro and in vivo. The MT-MOF TNS comprise non-centrosymmetric secondary building units of Mn-Ti-oxo cyclic octamers with charge heterogeneous components for piezoelectricity. The MT-MOF TNS promotes strong sonocavitation to induce piezoelectric effect with a high SP voltage (2.9 V) in situ, to directly excite charges, which is validated by SP-excited luminescence spectrometry. The SP voltage and charges depolarize the mitochondrial and plasma membrane potentials and cause ROS overproduction and serious tumor cell damage. Importantly, MT-MOF TNS can be decorated with targeting molecules and chemotherapeutics for more severe tumor regression by combining SPDT with chemodynamic therapy and chemotherapy. This report develops a fascinating MT-MOF piezoelectric nano-semiconductor and provides an efficient SPDT strategy for tumor treatment.

Positive Feedback Regulation of Circular RNA Hsa_circ_0000566 and HIF-1α promotes Osteosarcoma Progression and Glycolysis Metabolism.

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.

MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis.

The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1ß/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1ß/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA.

Comparison of Conservative Treatment and Surgery Treatment for Acute Scaphoid Fracture: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This meta-analysis aimed to investigate the effectiveness of conservative and surgical treatments of scaphoid fracture. METHODS: The literature databases of Pubmed, Cochrane library, and Embase were searched in March 2022. This work extracted the data based on healing time, grip strength, range of wrist motion, nonunion, time before returning to work, and complications (including persistent pain, malunion of the fracture, wound infection, scar sensitivity, hypertrophic scar, and implant-related complications). Stata 14.0 software was used for statistical analysis. RESULTS: Twelve RCTs studies met our inclusion criteria. The surgical group had a shorter healing-time and time before returning to work than the conservative group. In addition, the surgical group had significantly better grip strength and range of wrist motion than the conservative group (P < 0.01). However, there was no significant difference between nonunion (P = 0.538) and complications (P = 0.661) between the two groups. CONCLUSION: This meta-analysis showed that surgical treatment of scaphoid fracture achieved better grip strength and range of wrist motion, and had a lower healing time and time before returning to work than the conservative treatment. The two treatments had similar results in nonunion and complications. Further RCTs were required for the research.

Preparation and characterization of chitosan/whey isolate protein active film containing TiO2 and white pepper essential oil.

Active packaging films are designed to improve quality and extend the food shelf life by incorporating functional active ingredients into biopolymer films. This study developed a bioactive film based on chitosan (CS) and whey isolated protein (WPI) incorporated with 0.01 wt% TiO2 and 0.1 wt% white pepper essential oil (WPEO). The physicochemical properties of the prepared film were also evaluated comprehensively. The results showed that water solubility and water vapor permeability of the film incorporated with TiO2 and WPEO were 25.09% and 0.0933 g mm m-2 h-1 KPa-1, respectively, which were significantly higher than those of other films (P < 0.05). In addition, the UV barrier properties of films incorporating TiO2 and WPEO have improved. The films were characterized by Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The FTIR results showed interactions between TiO2 and WPEO with CS/WPI compound, and the SEM results indicated a good incorporation of TiO2 into the composite films. The antioxidative and antibacterial properties of films were significantly enhanced by incorporating WPEO. According to results, the developed biocomposite film can be considered as a packaging material.

[Clinical application of acromion radiological classification in diagnosis and treatment of rotator cuff injury].

OBJECTIVE: To develop a new classification of acromion based on the subacromial impingement theory and the Rockwood tilt view. And explore the application value of the new classification in the diagnosis and treatment of rotator cuff tear. METHODS: The clinical data of 101 patients underwent shoulder arthroscopic surgery for impingement syndrome or rotator cuff tear from January to December 2017 were retrospectively analyzed. There were 34 males and 67 females, aged from 34 to 76 years with an average of (56.31±9.63) years old, course of disease from 2 to 12 months with average of 6 months. Preoperative radiographs of the routine anteroposterior view, Rockwood tilt view and the supraspinatus outlet view were obtained. Based on the subacromial impingement theory and Rockwood radiographs, the morphology of the acromion can be divided into three types:typeⅠ(flat type), typeⅡ(bump type), and type Ⅲ (impingement type). Two observers classified 101 shoulder Rockwood radiographs according to the new classification method and the supraspinatus Outlet radiographs according to the traditional acromial morphological classification method. Supraspinatus tendon injuries were classified into no tear, partial-thickness tear, and full-thickness tear according to the arthroscopic findings. Concordance test (Kappa value) between the inter-observer and intra-observer was carried out for the new classification method and the traditional classification method respectively. The rank sum test was used to compare the mean acromiohumeral distance(AHD) of the three acromion forms in the new acromion classification method. Spearman rank correlation test and Gamma method were used to analyze the correlation between the new acromion classification method and the degree of supraspinatus tendon tear. RESULTS: The inter-observer consistency analysis of the new classification system was significantly better than that of the traditional classification (0.827 vs 0.278), the intra-observer consistency analysis of the new classification system were also significantly better than that of the traditional classification (0.921 vs 0.448, 0.890 vs 0.539). There was no statistical significance in the AHD among three types of the new classification(H=2.186, P>0.05). In all 101 patients, the highest proportion of impingement type acromion was 45.5% (46 cases), followed by bump type acromion was 36.6% (37 cases), and flat type acromion was 17.8% (18 cases). The incidence of supraspinatus tendon tear in the patients with impingement type acromion was significantly higher than that of the other two types of acromion, there was a spearman rank correlation between the new acromion type and the degree of the supraspinatus tendon tear(rs=0.719, P<0.001). CONCLUSION: Rockwood radiographs of the shoulder can well display the anterolateral osteophytes of the acromion. The new acromion classification method based on Rockwood radiographs has high reliability and good reproducibility, in which impingement type of acromion is closely related to supraspinatus tendon tear. Compared with the traditional classification and AHD, the new classification method has more diagnostic value than for rotator cuff injury.

Adverse impact of elevated progesterone levels on human chorionic gonadotropin trigger day on blastocyst transfer outcomes in gonadotropin-releasing hormone agonist cycles.

OBJECTIVE: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles? STUDY DESIGN: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred. RESULTS: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer. CONCLUSION: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles.

Noninvasive remote-controlled nanomedicine by using electric field stimulation for in vivo effective cancer therapy.

Precision therapy has developed as an important strategy for cancer treatment. We have developed an external electric field (EF) controlled targeting drug delivery nanosystem (TDDS) for precision cancer therapy. The electric field responsive targeting drug delivery nanosystem (EFTDDS) is synthesized by functionalizing mesoporous silica with polynitrophenyl-methacrylamide-folate (PNMAFA). The functional molecules grafted in the mesopores effectively encapsulate the drugs in the EFTDDS and control the drug release by nitrylphenyl dipolar responding to electric field. The EFTDDS has achieved high electric field control as demonstrated by the promoted EF-responsive release and the low nonspecific leakage of the doxorubicin. Furthermore, when breast cancer xenograft models on nude mice were treated with EF-stimulated nanomedicine, the tumor-inhibition rate increases to 75%, which is 2.7 times as high as that without electric field stimulation. The EFTDDS is demonstrated biodegradable, biocompatible, and EF remotely controllable, represents excellent inhibiting effect on tumor in vivo, and might become a promising nanomedicine platform for electrodynamic therapy (EDT) in the potential clinical applications.

The relationship between serum oestrogen levels and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study.

BACKGROUND: This study aimed to explore the relationship between serum oestrogen (E2) levels before endometrial transformation and pregnancy outcomes of hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles, which has been investigated for years without any consensus. METHODS: A retrospective cohort study of 10,209 cycles HRT-FET cycles was conducted at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from March 2017 to December 2020. A smooth fitting curve was constructed to identify the relationship between serum E2 levels before endometrial transformation and the clinical pregnancy rate. Then, threshold and saturation effect analysis was employed to explore the cut-off value of serum E2 levels. In addition, patients were divided into 2 groups based on their levels of serum E2 measured before progesterone-induced endometrial transformation: Group 1, < 300 pg/mL (n = 6251) and Group 2, ≥ 300 pg/mL (n = 3958). The clinical pregnancy and miscarriage rates of all groups were compared. Further smooth fitting curve analysis was employed by different subgroups segmented according to different endometrial thicknesses. RESULTS: When the serum E2 level was greater than 300 pg/mL, the clinical pregnancy rate decreased significantly (62.9% vs. 59.8%, p < 0.01), but the miscarriage rates were similar (13.5% vs. 15.6%, p = 0.14). While serum E2 level reached or exceeded 1400 pg/mL, there was no significant correlation between the clinical pregnancy rate and E2 level. The clinical pregnancy rate reached its higher level at lower E2 levels, regardless of the different endometrail thicknesses. CONCLUSIONS: Patients with a lower pretransformation serum E2 level (less than 300 pg/mL) have a higher clinical pregnancy rate and there was no correlation between the clinical pregnancy rate and a higher serum E2 level (greater than 1400 pg/mL) in HRT-FET cycles.

Clinical efficacy of arthroscopic treatment in ischial tuberosity cyst: A retrospective comparison study.

ABSTRACT: Ischial tuberosity cyst is a common disease, and the conventional incision procedure is associated with several disadvantages, leading to unsatisfactory therapeutic outcomes. The aim of the study was to evaluate the clinical outcomes of arthroscopic treatment for ischial tuberosity cyst and compared it with conventional incision surgery.The clinical data of 57 patients with ischial tuberosity cyst from May 2016 to September 2018 were retrospectively analyzed. According to the inclusion and exclusion criteria, a total of 49 patients were included. Of these patients, 24 patients received arthroscopic procedure (N = 24) and 25 patients received conventional incision procedure (N = 25). The operation time, intraoperative blood loss, postoperative drainage, postoperative hospital stay, and postoperative complications were compared between the 2 groups. Visual analogue scale scores was used to evaluate pain at 1 day, 1 week, and 1 month after the surgery.All 49 patients were followed up for (11.3 ±â€Š3.3) months. All patients in the arthroscopy group achieved phase I healing while 3 patients in conventional incision group developed complications. The operation time, intraoperative blood loss, postoperative drainage, and hospital stay in the arthroscopy group were (54.7 ±â€Š7.7) minutes, (20.8 ±â€Š3.5) mL, (20.3 ±â€Š5.6) mL, and (2.8 ±â€Š0.6) days, and were significantly better than those of (71.8 ±â€Š8.8) minutes, (67.3 ±â€Š12.0) mL, (103.6 ±â€Š20.3) mL, and (7.8 ±â€Š2.9) days in the conventional incision group, respectively. In the arthroscopy group, the visual analogue scale scores at 1 day, 1 week, and 1 month after the surgery [(2.6 ±â€Š0.7), (0.5 ±â€Š0.6), (0.3 ±â€Š0.5) points] were significantly lower than those in the conventional incision group [(6.0 ±â€Š0.7), (3.0 ±â€Š1.0), and (1.1 ±â€Š1.0) points], and the differences were statistically significant (P < .05). Finally, no significant difference was observed in the incidence of postoperative complications between the 2 groups (P > .05).In the treatment of ischial tuberosity cysts, arthroscopy has advantages of minimal invasion, less blood loss during perioperative period, milder postoperative pain, and rapid recovery when compared with conventional incision surgery.

A novel nomogram predicting cancer-specific survival in small cell lung cancer patients with brain metastasis.

Background: Brain metastasis (BM) is one of the most common metastatic sites in patients with small cell lung cancer (SCLC), and the prognosis remains very poor. This study aimed to establish a novel nomogram for predicting the cancer-specific survival (CSS) in SCLC patients with BM. Methods: SCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively collected. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors, which were further used to construct the prognostic nomogram. The discrimination and calibration of nomogram were evaluated by concordance index (C-index), receiver operating characteristic (ROC) curve, the area under ROC curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness. Kaplan-Meier survival curve was applied to analyze the survival outcome. Results: A total of 2,462 patients were enrolled in this study, and randomly assigned into training cohort (n=1,723) and validation cohort (n=739). Age, N stage, surgery, radiation, chemotherapy, bone metastasis, liver metastasis and lung metastasis were identified as independent prognostic factors of CSS. The C-indexes of nomogram was 0.683 [95% confidence interval (CI): 0.667-0.699] in the training cohort, and 0.659 (95% CI: 0.634-0.684) in the validation cohort. The AUC values of 6-, 9- and 12-month CSS were 0.723, 0.742 and 0.737 respectively in the training cohort, while 0.715, 0.737 and 0.739 in the validation cohort. The ROC, calibration and DCA curves showed good discrimination, calibration and clinical applicability of this nomogram in predicting prognosis. Moreover, patients in high-risk group had a worse survival outcome than patients in medium-risk and low-risk groups. Conclusions: A novel nomogram was constructed and validated for predicting individual prognosis in SCLC patients with BM. This nomogram could help clinicians make effective treatment strategies for patients.

[Arthroscopic treatment for the calcific tendinitis at soft tissues around hip].

OBJECTIVE: To explore the feasibility and clinical effects of arthroscopic treatment for the calcific tendinitis at soft tissues around hip. METHODS: A total of 16 patients diagnosed as the calcific tendinitis at soft tissues around hip from May 2013 to July 2018 were retrospectively analyzed. All the 16 patients received arthroscopic procedures. There were 10 males and 6 females with an average age of 35 to 63 (44.50±6.67) years old and 9 left hips, 6 right hips were involved. The course of disease were 1 to 8(3.18±1.97) days. Clinical effects were evaluated with visual analogue scale(VAS), modified Harris hip scores (HHS), nonarthritic hip score (NAHS) and imaging examinations before operation, 1 day after operation and the final follow-up. RESULTS: All 16 patients successfully finished the arthroscopic procedures in 0.5 to 1.2 (0.75±0.21) hours. Primary healing of incision were obtained without any complications of infection, wound hematocele and neurovascular injury. All 16 patients received an average postoperative follow-up of 6 to 12 (9.6±2.3) months. Before operation, the VAS were 7.88±0.72, modified HHS were 29.25±3.23, NAHS were 27.42±3.08. The 1st day postoperative VAS were 2.19±0.66, modified HHS were 82.56± 5.64, NAHS were 82.11±2.94, all the difference were statistically significant between before and 1 day after operation (P< 0.05). At the final follow-up, the VAS were 0.38±0.50, modified HHS were 94.31±2.82, NAHS were 94.84±2.85, all the scores were improved significantly compared to that before operation (P<0.05). At final follow-up, there was no recurrence and the calcification disappeared in all patients, there was one patient feel sourness around the hip. CONCLUSION: Arthroscopic treatment for the calcific tendinitis at soft tissues around hip is effective.It has advantages of minimal invasive, rapid pain relief, rapid hip joint function recovery and definite clinical effects.

Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors.

Hypoxia has been firmly correlated to the drug resistance of solid tumors. Alleviation of hypoxia by tumor reoxygenation is expected to sensitize the chemotherapy toward solid tumors. Alternatively, ferroptosis provides a therapeutic strategy to overcome apoptotic resistance and multidrug resistance of solid tumors, collaboratively strengthening the chemotherapy toward hypoxic tumors. Herein, an ultrasound (US)-activatable nanomedicine was developed for overcoming hypoxia-induced resistance to chemotherapy and efficiently inhibiting tumor growth by inducing sensitized apoptosis and collaborative ferroptosis of tumor cells. This nanomedicine was constructed by integrating ferrate and doxorubicin into biocompatible hollow mesoporous silica nanoplatforms, followed by assembling a solid-liquid phase-change material of n-heneicosane. The US-induced mild hyperthermia initiates the phase change of n-heneicosane, enabling US-activated co-release of ferrate and doxorubicin. Results reveal that the released ferrate effectively reacts with water as well as the over-expressed hydrogen peroxide and glutathione in tumor cells, achieving tumor-microenvironment-independent reoxygenation and glutathione-depletion in tumors. The reoxygenation down-regulates expressions of hypoxia-inducible factor 1α and multidrug resistance gene/transporter P-glycoprotein in tumor cells, sensitizing the apoptosis-based doxorubicin chemotherapy. More importantly, exogenous iron metabolism from the nanomedicine initiates intracellular Fenton reactions, leading to reactive oxygen species overproduction and iron-dependent ferroptotic death of tumor cells. Furthermore, the glutathione-depletion inactivates the glutathione peroxidase 4 (GPX4, a critical regulatory target in ferroptosis), inhibiting the reduction of lipid peroxides and reinforcing the ferroptotic cell death. The sensitized chemotherapy together with the iron-dependent ferroptosis of tumor cells play a synergistic role in boosting the growth suppression of hypoxic osteosarcoma in vivo. Additionally, the nanomedicine acts as a nanoprobe for in vivo photoacoustic imaging and glutathione tracking, showing great potential as theranostic agents for hypoxic solid tumors treatment.

[Arthroscopic repair with footprint ending shift for massive rotator cuff tear].

OBJECTIVE: To investigate the method and clinical effects of arthroscopic rotator cuff repair with footprint ending shift for massive rotator cuff tear. METHODS: From March 2015 to April 2019, 27 patients with massive rotator cuff tear underwent arthroscopic repair, including 12 males and 15 females, ranging in age from 37 to 74 years old, with an average age of (56.1±8.9) years. According to the tension of rotator cuff, 5 patients were treated with double row suture bridge technique, and 22 patients were treated with single row technique, among which 7 patients underwent partial rotator cuff repair. Before and after operation, University of California Los Angeles(UCLA) score, American Shoulder and Elbow Surgeons (ASES) score and visual analogue scale (VAS) were used to evaluate shoulder joint function. RESULTS: All the patients were followed up, and the duration ranged from 8 to 40 months, with an average of (18.0±5.9) months. The UCLA score increased from preoperative 8.67±0.78 to final follow-up 30.89±1.07(t=43.56, P<0.001);ASES score increased from preoperative 8.56±0.67 to final follow-up 12.63±0.33(t=15.28, P<0.001);and the VAS decreased from preoperative 6.00(5.00 to 7.00) scores to final follow-up 0.00 (0.00 to 2.00) scores (Z=-4.56, P<0.001). Three patients could not lift the shoulder above the head, without pain. The symptom had no effects on daily work and life, 2 of these patients underwent partial rotator cuff repair. CONCLUSION: Arthroscopic rotator cuff repair with footprint ending shift for massive rotator cuff tear has satisfactory results, and single-row can be chosen to completely or partial repair rotator cuff tear for most patients.

Downregulation of XIST ameliorates acute kidney injury by sponging miR-142-5p and targeting PDCD4.

Acute kidney injury (AKI) is a common kidney disease that markedly affects public health. To date, the roles of long noncoding RNA XIST in AKI are poorly understood. Here, we investigated the biological functions of XIST in AKI. We observed that XIST expression increased in patients with AKI and HK-2 cells stimulated by CoCl2 . In addition, a rat AKI model induced by ischemia-reperfusion was established. Tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 messenger RNA expression were induced in vivo; moreover, XIST expression was upregulated. Knockdown of XIST significantly repressed CoCl2 -triggered injury in HK-2 cells. However, microRNA (miR)-142-5p, a downstream target of XIST, was downregulated in AKI. miR-142-5p was repressed by XIST and miR-142-5p could inhibit CoCl2 -induced injury in HK-2 cells. Moreover, PDCD4 expression was significantly increased in AKI. PDCD4 was predicted to be the target of miR-142-5p. Subsequently, loss of PDCD4 was able to retard injury in HK-2 cells exposed to CoCl2. Thus, we suggest that XIST regulates miR-142-5p and PDCD4, and it has the potential to function as a biomarker in therapeutic strategies for AKI.