A case report of adolescent lactation due to the drug blonanserin.

BACKGROUND: Second-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients, which should not be underestimated. CASE PRESENTATION: We report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient's psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed. CONCLUSIONS: Although Blonanserin's clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists' choice of antidepressant therapy in combination with antipsychotic drugs.

Differences in the effectiveness of leukocyte-rich platelet-rich plasma compared with leukocyte-poor platelet-rich plasma in the treatment of rotator cuff surgery: an umbrella review of meta-analyses.

BACKGROUND: An umbrella review of meta-analyses was conducted to evaluate the use of platelet-rich plasma (PRP) in arthroscopic surgeries of rotator cuff injury. The effectiveness of leukocyte-poor PRP and leukocyte-rich PRP in the treatment of rotator cuff surgery was also compared. METHODS: Web of Science, Embase, PubMed/MEDLINE, and the Cochrane Library were searched from inception to May 2024. Literature screening, quality evaluation, and data extraction were performed according to the inclusion and exclusion criteria. The Jadad decision algorithm was used to ascertain which meta-analysis represented the best evidence. RESULTS: A total of 11 meta-analyses with evidence level ranging from level 1 to 2 were included in this umbrella review. Leukocyte-poor PRP was effective in reducing rotator cuff retear rates, alleviating pain, and increasing Constant scores compared with non-PRP treatments. However, it did not show improvement on the University of California Los Angeles (UCLA) score, the American Shoulder and Elbow Surgeons (ASES) score, and the Simple Shoulder Test (SST) compared with the non-PRP treatment group. Meanwhile, the leukocyte-rich PRP group improved the SST but showed no different results when compared with the non-PRP treatment group. CONCLUSION: Compared with no use of PRP, leukocyte-poor PRP was able to alleviate postoperative pain, reduce the retear rate, and improve the postoperative Constant score. Leukocyte-rich PRP could effectively enhance postoperative SST outcomes, leading to improvement of patient satisfaction and quality of life. Future researches should prioritize long-term follow-up studies and evaluate the durability of these results.

Core decompression combined with bone marrow mononuclear cells in the treatment of femoral head necrosis: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis is controversial. The purpose of this study was to conduct a meta-analysis and systematic review of the evaluation of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis, and to compare the therapeutic effect of this method with that of core decompression alone, so as to provide a basis for subsequent research and clinical treatment. METHODS: We conducted detailed searches across four databases in Embase, PubMed, Web of Science, and the Cochrane Library (up to October 2023), including eight studies with a total of 370 participants and 491 hip cases. This meta-analysis followed the Preferred Reporting Project (PRISMA) guidelines. Review Manager 5.4 was used to summarize and analyze the outcome indicators and the quality and reliability of the MAs were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). RESULTS: Eight studies were included inclusion criteria. The results of meta-analysis showed that the therapeutic effect of CD combined with BMMC on VAS was better than that of CD alone (MD =-5.32, 95%CI: -9.90, -0.74, P=0.02, I²=98%), and there was no statistically significant difference between CD combined with BMMC and CD alone in the treatment of HHS (MD =2.73, 95%CI: -2.63,8.09, P=0.32, I²=82%). We conducted sensitivity analysis, the results showed that CD joint BMMC treatment effect on the HHS is superior to the single CD (MD = 5.57, 95% CI: 1.94, 9.20, P = 0.003, I squared = 0%), both no significant differences in VAS (MD = 0.47, 95% CI: -1.74, 0.79, P=0.46, I²=83%). CONCLUSION: In this study, we found that core decompression combined with bone marrow monocyte therapy improved femoral head necrosis better than core decompression alone.

Extracorporeal shock wave therapy with imaging examination for early osteonecrosis of the femoral head: a systematic review.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) is a traditional non-invasive therapy to treat osteonecrosis of the femur head (ONFH). This systematic review aims to investigate whether ESWT can improve the clinical function of ONFH and whether differences in improvement can be observed in radiographic outcomes. MATERIALS AND METHODS: Two authors independently searched PubMed, Embase, Cochrane Library, and Web of Science for English articles until October 21, 2023. After screening and reading the literature, the two authors independently used corresponding scales to evaluate the quality of the included articles and extracted data. The key data extracted included the Harris Hip Score (HHS), Visual Analog Scale (VAS), changes in lesion size, the change in the Association Research Circulation Osseous (ARCO) stage, and bone marrow edema stage. RESULTS: Nine articles included 468 males and 248 females. The average age was 43.29 years and the mean follow-up time was 15.19 months. After receiving ESWT, five studies involving 146 hips showed a higher HHS (MD=-33.38; 95%CI, -46.31, -20.45), and the difference was statistically significant (P<0.00001). The average VAS before treatment was above 5, but it dropped to 1.2 after ESWT (MD=4.64; 95%CI, 3.63, 5.64), and the difference was statistically significant (P<0.00001). Three studies found no significant differences in the areas of femoral head necrosis before and after treatment with ESWT(MD=9.66; 95%CI, -0.36, 19.67; P=0.06; I2=84%). Two articles showed that the use of ESWT had no significant effect on the change in the ARCO stage (MD=1.11; 95%CI, 0.76, 1.62; P=0.60; I2=0%). Three studies indicated that using ESWT could improve the bone marrow edema symptom in the early stage of ONFH (MD=4.35; 95%CI, 1.32, 14.37; P=0.02; I2=62%). CONCLUSION: Based on the current evidence, ESWT shows promise as a therapy to enhance hip function and alleviate pain in the early stage of ONFH. With the advancement of more precise imaging techniques, ESWT can potentially reduce the area affected by ONFH. However, such reduction was not found to be statistically significant at the imaging level. Additionally, ESWT could improve symptoms of bone marrow edema in the early stage. However, no significant change in ARCO grade was observed with ESWT treatment.

The efficacy of extracorporeal shock wave therapy for knee osteoarthritis : an umbrella review.

BACKGROUND: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. RESULTS: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=-2.94, 95% CI: -5.52, -0.37, P=0.03, I²=60%], Visual Analog Scale (VAS) (MD=-2.0, 95% CI: -2.5, -1.5, P<0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P<0.00001, I²=0%), and Lequesne index (MD=-2.85, 95% CI: -3.64, -2.07, P<0.00001, I²=48%). CONCLUSION: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.

Highly Flexible, High-Performance, and Stretchable Piezoelectric Sensor Based on a Hierarchical Droplet-Shaped Ceramics with Enhanced Damage Tolerance.

Stretchable self-powered sensors are of significant interest in next-generation wearable electronics. However, current strategies for creating stretchable piezoelectric sensors based on piezoelectric polymers or 0-3 piezoelectric composites face several challenges such as low piezoelectric activity, low sensitivity, and poor durability. In this paper, a biomimetic soft-rigid hybrid strategy is used to construct a new form of highly flexible, high-performance, and stretchable piezoelectric sensor. Inspired by the hinged bivalve Cristaria plicata, hierarchical droplet-shaped ceramics are manufactured and used as rigid components, where computational models indicate that the unique arched curved surface and rounded corners of this bionic structure can alleviate stress concentrations. To ensure electrical connectivity of the piezoelectric phase during stretching, a patterned liquid metal acts as a soft circuit and a silicone polymer with optimized wettability and stretchability serves as a soft component that forms a strong mechanical interlock with the hierarchical ceramics. The novel sensor design exhibits excellent sensitivity and durability, where the open circuit voltage remains stable after 5000 stretching cycles at 60% strain and 5000 twisting cycles at 180°. To demonstrate its potential in heathcare applications, this new stretchable sensor is successfully used for wireless gesture recognition and assessing the progression of knee osteoarthritis.

Interleukin-33 Potentiates TGF-ß Signaling to Regulate Intestinal Stem Cell Regeneration After Radiation Injury.

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal radiation injury. Accumulating evidence indicates that the interleukin family members play critical roles in intestinal stem-cell-mediated epithelial regeneration. However, little is known about the relationship between interleukin 33 (IL-33)/ST2 axis and intestinal regeneration after radiation injury. We demonstrate here that IL-33 expression significantly increased after radiation treatment. Deficiency of IL-33/ST2 promotes intestinal epithelial regeneration, resulting in a reduction of mortality during radiation-induced intestine injury. Using ex vivo organoid cultures, we show that recombinant IL-33 promotes intestinal stem cell differentiation. Mechanistically, the effects of IL-33 were mediated by activation of transforming growth factor-ß signaling. Our findings reveal a fundamental mechanism by which IL-33 is able to regulate the intestinal crypt regeneration after tissue damage.

Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy.

There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

Assay establishment and validation of a high-throughput organoid-based drug screening platform.

BACKGROUND: Organoids are three-dimensional structures that closely recapitulate tissue architecture and cellular composition, thereby holding great promise for organoid-based drug screening. Although growing in three-dimensional provides the possibility for organoids to recapitulate main features of corresponding tissues, it makes it incommodious for imaging organoids in two-dimensional and identifying surviving organoids from surrounding dead cells after organoids being treated by irradiation or chemotherapy. Therefore, significant work remains to establish high-quality controls to standardize organoid analyses and make organoid models more reproducible. METHODS: In this study, the Z-stack imaging technique was used for the imaging of three-dimensional organoids to gather all the organoids' maximum cross sections in one imaging. The combination of live cell staining fluorescent dye Calcein-AM and ImageJ assessment was used to analyze the survival of organoids treated by irradiation or chemotherapy. RESULTS: We have established a novel quantitative high-throughput imaging assay that harnesses the scalability of organoid cultures. Using this assay, we can capture organoid growth over time, measure multiple whole-well organoid readouts, and show the different responses to drug treatments. CONCLUSIONS: In summary, combining the Z-stack imaging technique and fluorescent labeling methods, we established an assay for the imaging and analysis of three-dimensional organoids. Our data demonstrated the feasibility of using organoid-based platforms for high-throughput drug screening assays.

Preparation and Properties of an Ultrahigh-Energy-Density Aqueous Supercapacitor with a Superconcentrated Electrolyte and a Sr-Modified Lanthanum Zirconate Flexible Electrode.

Although supercapacitors are considered to play a vital role in flexible electronic devices, there are still some problems that need to be overcome, such as low energy density and narrow electrochemical stability windows in aqueous electrolytes. Herein, we have successfully synthesized a series of Sr-modified La2Zr2O7 (LZO-x) nanofibers as a new electrode material by a facile electrospinning technique. To determine the best doping sample, the changes in structures and electrochemical performances of La2Zr2O7 (LZO-x) nanofibers with various Sr contents are investigated carefully. Then, the LZO-0.2 sample shows the highest capacitance (1445 mF·cm-2). Furthermore, we also develop a low-cost superconcentrated electrolyte, which achieves a wide electrochemical stability window of 2.7 V using a working electrode (LZO-0.2). Finally, we use the LZO-0.2 electrode and the superconcentrated electrolyte to fabricate a flexible supercapacitor device, which shows an excellent capacitance of 175 F·g-1 at a current density of 1.15 A·g-1. Moreover, the aqueous device has excellent cycle stability and outstanding flexibility, and the energy density of this device is 177.2 Wh·kg-1 and the corresponding power density is 1557.7 W·kg-1.

CBP/P300 Inhibitors Mitigate Radiation-Induced GI Syndrome by Promoting Intestinal Stem Cell-Mediated Crypt Regeneration.

PURPOSE: Radiation-induced gastrointestinal syndrome (RIGS) is currently the main cause of death for people exposed to a high dose of irradiation during nuclear incidents, and there is currently no approved effective therapy. Here, we found that CBP/P300 inhibitors, with high efficacy and low toxicity, might be promising radiation mitigators that can cure RIGS. METHODS AND MATERIALS: Ex vivo 3D organoid cultures derived from mouse jejunum and human ileum and colon were used to examine the radio-mitigative effects of CBP/P300 inhibitors. The radio-mitigative effect was evaluated by quantifying the survival rate and size of organoids after radiation. SGC-CBP30 (50 mg/kg body weight), an inhibitor of CBP/P300, was intraperitoneally injected into C57B/6J mice 24 hours after subtotal-body irradiation or whole-body irradiation. The regenerated crypts and animal survival were determined by microcolony assay and the Kaplan-Meier method, respectively. Lgr5-lacZ mice were used to evaluate the survival of intestinal stem cells after treatments. RESULTS: We found that CBP/P300 inhibitors were effective mitigators that could be used to treat RIGS. CBP/P300 inhibition promoted the regeneration of intestinal organoids in vitro and of crypts in vivo. Remarkably, the administration of CBP/P300 inhibitors to mice 24 hours after lethal irradiation promoted Lgr5+ intestinal stem cell and crypt recovery, resulting in improved mouse survival. Moreover, our data show that CBP/P300 inhibitors rescued irradiated mice from RIGS by delaying intestinal epithelial cell cycle progression after radiation. CONCLUSIONS: These data demonstrate that CBP/P300 inhibitors are effective medical countermeasures to mitigate gastrointestinal toxicity from radiation.

SIRT1 inhibitors mitigate radiation-induced GI syndrome by enhancing intestinal-stem-cell survival.

High-dose radiation exposure induces gastrointestinal (GI) stem cell death, resulting in denudation of the intestinal mucosa and lethality from GI syndrome, for which there is currently no effective therapy. Studying an intestinal organoid-based functional model, we found that Sirtuin1(SIRT1) inhibition through genetic knockout or pharmacologic inhibition significantly improved mouse and human intestinal organoid survival after irradiation. Remarkably, mice administered with two doseages of SIRT1 inhibitors at 24 and 96 h after lethal irradiation promoted Lgr5+ intestinal stem cell and crypt recovery, with improved mouse survival (88.89% of mice in the treated group vs. 0% of mice in the control group). Moreover, our data revealed that SIRT1 inhibition increased p53 acetylation, resulting in the stabilization of p53 and likely contributing to the survival of intestinal epithelial cells post-radiation. These results demonstrate that SIRT1 inhibitors are effective clinical countermeasures to mitigate GI toxicity from potentially lethal radiation exposure.

Metformin chlorination byproducts in drinking water exhibit marked toxicities of a potential health concern.

Metformin (MET), a worldwide used drug for type 2 diabetes, has been found with the largest amount by weight among all drugs in aquatic environment, including the drinking water systems where this emerging micropollutant is inevitably transformed during chlorination process. Whether MET chlorination byproducts Y (C4H6ClN5) and C (C4H6ClN3) exist in drinking water remains unknown. Although MET has health-promoting properties, whether or how its chlorination byproducts affect health is still uncharacterized. Here we reveal that MET and byproduct C are present in worldwide drinking water with the highest doses detected for MET and C as 1203.5 ng/L and 9.7 ng/L respectively. Under simulated chlorination conditions, we also demonstrate that both byproducts can be increasingly produced with increment of MET concentration, suggesting a hidden threat on the safety and sustainability of global water supply. Through systematic evaluations, we demonstrate that MET chlorination byproducts Y and C exhibit toxicities instead of genotoxicity to live worms and human HepG2 cells at millimolar doses. Moreover, both byproducts are harmful to mice and particularly Y at 250 ng/L destroys the mouse small intestine integrity. Unprecedentedly, we unveil boiling and activated carbon adsorption as effective alternative solutions that may be in urgent demand globally for removing these byproducts from drinking water.

Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells.

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury, although the repair mechanisms are unclear. Here, we found that Bach2 deficiency promotes intestinal epithelial cell proliferation during homeostasis. Moreover, genetic inactivation of Bach2 in mouse intestinal epithelium facilitated crypt regeneration after irradiation, resulting in a reduction in mortality. RNA-sequencing analysis of isolated crypts revealed that Bach2 deficiency altered the expression of numerous genes, including those regulating double-strand break repair. Mechanistic characterizations indicated that Bach2 deletion facilitated DNA repair in intestinal crypt cells, as evidenced by faster resolution of γ-H2AX and 53BP1 foci in Bach2-/- crypt cells, compared with Bach2+/+ control. Together, our studies highlight that Bach2 deficiency promotes intestinal regeneration by accelerating DNA repair in intestinal stem cells after radiation damage.

Organoid based personalized medicine: from bench to bedside.

Three-dimensional cultured organoids have become a powerful in vitro research tool that preserves genetic, phenotypic and behavioral trait of in vivo organs, which can be established from both pluripotent stem cells and adult stem cells. Organoids derived from adult stem cells can be established directly from diseased epithelium and matched normal tissues, and organoids can also be genetically manipulated by CRISPR-Cas9 technology. Applications of organoids in basic research involve the modeling of human development and diseases, including genetic, infectious and malignant diseases. Importantly, accumulating evidence suggests that biobanks of patient-derived organoids for many cancers and cystic fibrosis have great value for drug development and personalized medicine. In addition, organoids hold promise for regenerative medicine. In the present review, we discuss the applications of organoids in the basic and translational research.

Preparation of Y-Doped La2Ti2O7 Flexible Self-Supporting Films and Their Application in High-Performance Flexible All-Solid-State Supercapacitor Devices.

Flexible all-solid-state supercapacitors have drawn more attention owing to the rapid growth of wearable electronic equipments. Herein, we have succeeded in synthesizing a series of Y-doped lanthanum titanate flexible self-supporting films (LSF-x, 0.1 ≤ x ≤ 0.5) and investigating the change of microstructures, morphological characteristics, and lattice structures of these films affected by different Y-doping contents. To further determine the optimum Y-doping content, we have explored the electrochemical properties of working electrodes prepared by LSF-x (0.1 ≤ x ≤ 0.5) samples as the main active material. As the LSF-0.2 electrode has the best areal capacitance of 1.3 F·cm-2 at 2 mA·cm-2, we use the LSF-0.2 electrodes and PVA-Na2SO4 gel to fabricate a flexible all-solid-state supercapacitor device. This device has a high areal capacitance of 255.9 mF·cm-2 at a current density of 2 mA·cm-2 with a high cell voltage of 2.1 V, while the corresponding energy density is 156.8 µWh·cm-2 with a power density of 2.1 mW·cm-2. Moreover, it also shows a long cycling life and outstanding flexibility. Therefore, the LSF-0.2 sample can be used as an excellent energy-storage material for a wearable electronic device.

The Application of a Y-Modified Lanthanum Zirconate Flexible Thin Film for a High-Performance Flexible Supercapacitor.

With the rapid development of wearable electronics devices, there is increasing demand for the development of new flexible energy storage devices with high security, and this has become a hot research topic. Although flexible supercapacitors are considered to be high-performance energy-storage equipment because of their fast charging/discharging ability, long cycle life, good reliability, wide operating temperature range, and so on, there are still many drawbacks that need to be overcome. Herein, the La2 Zr2 O7 (LZO) thin film is synthesized as a new energy-storage material by using a facile electrospinning method and calcination at low temperature. In addition, the mechanism of producing the flexibility of this film is determined by TG, IR, and XRD analyses. As previous studies have suggested that the charge storage of the LZO film can be attributed to the mechanism of oxygen intercalation, the Y element is doped into the LZO film to increase the concentration of oxygen vacancies. The changes in structural and electrochemical properties of La2 Yx Zr2-x O3 (0≤x≤0.5) nanofibers (LNF-x) with increasing Y content are studied carefully to obtain the best doping sample. The LNF-0.1 sample shows the highest areal capacitance of 605.3 mF cm-2 at 2 mA cm-2 , so a symmetrical flexible device is fabricated with LNF-0.1 electrodes. This device has a high energy density (76.7 µW h cm-2 at 2 mW cm-2 ), good cycling stability, and excellent mechanical flexibility. This study thus provides a new research trend for portable and wearable electronics.

Inhibition of SIRT1 promotes taste bud stem cell survival and mitigates radiation-induced oral mucositis in mice.

Taste loss is one of the debilitating complications in radiation-induced oral mucositis (RIOM), as occurs in head and neck cancer patients undergoing radiotherapy. We report here a radio-mitigation effect of Sirtuin 1 (SIRT1) inhibitors in taste bud organoids and a mouse model of radiation-induced taste bud injury. The organoids, developed from circumvallate (CV) papilla, were irradiated with single dose of X-rays and inhibitors of SIRT1 or SIRT2 were added 24 h later. The survival was evaluated by measuring the number and size of regenerated organoids after irradiation (IR). Oral mucositis (OM) was induced by IR of the oral region of Lgr5-lacZ transgenic mice. The surviving Lgr5+ taste bud stem cells were identified after lacZ-staining and the mucosal ulceration on tongue dorsal surface was determined by histological methods. Results showed that SIRT1 inhibitors (nicotinamide, EX527, salermide and sirtinol), but not SIRT2 inhibitors, significantly improve taste bud organoid survival after IR. Remarkably, administration of nicotinamide (NAM), a recognized inhibitor of SIRT1 to mice 24 h after IR promotes the survival of Lgr5+ taste bud stem cells, resulting in alleviated tongue mucositis. In conclusion, SIRT1 inhibitors promote Lgr5+ taste bud stem cell survival and mitigate RIOM in mice. These observations have important implications for efforts to develop therapeutic strategies against taste dysfunction and mucosal ulceration in RIOM.

Activated B Lymphocyte Inhibited the Osteoblastogenesis of Bone Mesenchymal Stem Cells by Notch Signaling.

Estrogen is very important to the differentiation of B lymphocytes; B lymphopoiesis induced by OVX was supposedly involved in osteoporosis. But the effects of B lymphocytes on the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) are not clear. In this study, we detected bone quality and bone loss in a trabecular bone by electronic universal material testing machine and microcomputed tomography (micro-CT) in OVX and splenectomized-ovariectomy (SPX-OVX) rats. Additionally, changes in lymphocytes (B lymphocyte, CD4+ and CD8+ T lymphocytes, and macrophages) in the bone marrow were analyzed by flow cytometry. The osteogenesis of BMSCs cocultured with normal and LPS-pretreated B lymphocytes was detected by BCIP/NBT and Alizarin red S staining. Measurement of the Notch2, Notch4, Hey1, Hey2, Hes1, and runt-related transcription factor 2 (Runx2) expression in BMSCs cocultured with B lymphocytes was done using real-time PCR. The effects of dexamethasone and DAPT (inhibitor of Notch signaling) on osteogenesis of BMSCs were detected by BCIP/NBT, Alizarin red S staining, and real-time PCR. Osteoporosis happened in OVX rats, more serious in SPX-OVX rats, B lymphocytes increased in OVX rats, and sharply higher in SPX-OVX rats. Osteoporosis did not happen in SPX rats which is still companied with a high increase of B lymphocytes. LPS-pretreated B lymphocytes suppressed the osteogenesis of BMSCs, but the normal B lymphocytes could not. The LPS-pretreated B lymphocytes upregulated the expression of Notch4, Hes1, and Hey2 and downregulated the expression of Runx2 in BMSCs. Dexamethasone and DAPT could downregulate the high expression of Notch4, Hes1, Hey2 and upregulate the low expression of Runx2 in BMSCs which cocultured with LPS treated B lymphocytes, the inhibited ALP and Alizarin red staining in BMSCs which cocultured with LPS treated B lymphocytes also partly restored.

Platelet count on preoperative day 1 predicts the long-term responses to laparoscopic splenectomy for Chinese patients with medically refractory idiopathic thrombocytopenic purpura.

BACKGROUND: Laparoscopic splenectomy (LS) is regarded as a second-line treatment for medically refractory idiopathic thrombocytopenic purpura (ITP), but the predictive factors for the long-term postoperative responses to ITP are still a matter of debate. We aimed to investigate the factors that can predict the long-term response after LS for Chinese patients with medically refractory ITP. METHODS: From January 2011 to September 2016, 78 Chinese patients with ITP who underwent LS were retrospectively analyzed. Twelve parameters were analyzed by univariate and multivariate methods. RESULTS: Univariate analysis revealed that platelet count on preoperative day (PRD) 1 (P < 0.001) and operative time (P = 0.011) were significantly associated with long-term response of ITP after LS. Multivariate analysis revealed that platelet count on PRD 1 was a predictive factor of long-term response (P < 0.001). Furthermore, a long-term, stable response of platelet count on PRD 1 of > 30.0 × 109/L was easier to achieve than a platelet count on PRD 1 ≤ 30.0 × 109/L after LS for ITP. CONCLUSIONS: LS is a valuable and effective option in the treatment of medically refractory ITP. Platelet count on PRD 1 is an independent predicting factor for long-term response after LS for Chinese patients with ITP.