A retrospective study of ovarian tissue cryopreservation in female patients with hematological diseases for fertility preservation.

PURPOSES: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. METHODS: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. RESULTS: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. CONCLUSIONS: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.

Age and aging process alter the gut microbes.

BACKGROUND: Gut microbes and age are both factors that influence the development of disease. The community structure of gut microbes is affected by age. OBJECTIVE: To plot time-dependent gut microbe profiles in individuals over 45 years old and explore the correlation between age and gut microbes. METHODS: Fecal samples were collected from 510 healthy individuals over 45 years old. Shannon index, Simpson index, Ace index, etc. were used to analyze the diversity of gut microbes. The beta diversity analysis, including non-metric multidimensional scaling (NMDS), was used to analyze community distribution. Linear discriminant analysis (LDA) and random forest (RF) algorithm were used to analyze the differences of gut microbes. Trend analysis was used to plot the abundances of characteristic gut microbes in different ages. RESULTS: The individuals aged 45-49 had the highest richness of gut bacteria. Fifteen characteristic gut microbes, including Siphoviridae and Bifidobacterium breve, were screened by RF algorithm. The abundance of Ligiactobacillus and Microviridae were higher in individuals older than 65 years. Moreover, the abundance of Blautia_A massiliensis, Lubbockvirus and Enterocloster clostridioformis decreased with age and the abundance of Klebsiella variicola and Prevotella increased with age. The functional genes, such as human diseases and aging, were significantly different among different aged individuals. CONCLUSIONS: The individuals in different ages have characteristic gut microbes. The changes in community structure of gut microbes may be related to age-induced diseases.

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Elevator block brake structural optimization design based on an approximate model.

An Aquila optimizer-back propagation (AO-BP) neural network was used to establish an approximate model of the relationship between the design variables and the optimization objective to improve elevator block brake capabilities and achieve a lightweight brake design. Subsequently, the constraint conditions and objective functions were determined. Moreover, the multi-objective genetic algorithm optimized the structural block brake design. Finally, the effectiveness of the optimization results was verified using simulation experiments. The results demonstrate that the maximum temperature of the optimized brake wheel during emergency braking was 222.09°C, which is 36.71°C lower than that of 258.8°C before optimization, with a change rate of 14.2%. The maximum equivalent stress after optimization was 246.89 MPa, 28.87 MPa lower than that of 275.66 MPa before optimization, with a change rate of 10.5%. In addition, the brake wheel mass was reduced from 58.85 kg to 52.40 kg, and the thermal fatigue life at the maximum equivalent stress increased from 64 times before optimization to 94 times after optimization.

Analysis of changes in high-mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure.

We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.

Mesenchymal stromal cell biotherapy for Parkinson's disease premotor symptoms.

Parkinson's disease (PD) is a neurodegenerative disorder with motor deficits due to nigrostriatal dopamine depletion and with the non-motor/premotor symptoms (NMS) such as anxiety, cognitive dysfunction, depression, hyposmia, and sleep disorders. NMS is presented in at least one-fifth of the patients with PD. With the histological information being investigated, stem cells are shown to provide neurotrophic supports and cellular replacement in the damaging brain areas under PD conditions. Pathological change of progressive PD includes degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain. The current stem cell beneficial effect addresses dopamine boost for the striatal neurons and gliovascular mechanisms as competing for validated PD drug targets. In addition, there are clinical interventions for improving the patient's NMS and targeting their autonomic dysfunction, dementia, mood disorders, or sleep problems. In our and many others' research using brain injury models, multipotent mesenchymal stromal cells demonstrate an additional and unique ability to alleviate depressive-like behaviors, independent of an accelerated motor recovery. Intranasal delivery of the stem cells is discussed for it is extensively tested in rodent animal models of neurological and psychiatric disorders. In this review, we attempt to discuss the repairing potentials of transplanted cells into parkinsonism pathological regions of motor deficits and focus on preventive and treatment effects. From new approaches in the PD biological therapy, it is believed that it can as well benefit patients against PD-NMS.

De novo domestication: a new way for crop design and breeding.

The impending global climate change presents significant challenges to agricultural production. It is imperative to find approaches to ensure sustained growth in food production while reducing agricultural input, in order to meet the needs of worldwide people for nutritious food supply. One of the effective strategies to address this challenge is still the development of new crop varieties with high yield, stable yield, environmental friendliness and rich nutrition. The creation of new crop cultivars depends largely on the expansion of genetic resources and the innovation of breeding techniques. De novo domestication is an innovative breeding strategy for developing new crop varieties. It involves utilizing undomesticated or semi-domesticated plants with desirable traits as founder species for breeding. The process involves rapid domestication of wild plants through the redesign of agronomic traits and the introduction of domestication genes to meet diverse human needs. In this review, we overview the history of crop domestication and genetic improvement, clarify the necessity of enriching crop diversity, and emphasize the significance of wild plants' genetic diversity in expanding the scope for crop redesign. Breeding strategy innovation is the key to accelerate crop breeding. We also discuss the feasibility and prospects of rapid developing new crops through de novo domestication.

Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer.

BACKGROUND: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer. METHODS: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors. RESULTS: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value. CONCLUSION: This model may promote risk stratification and individualized treatment, thus improving the prognosis.

Mechanisms of myocardial ischemic injury repair by bone marrow mesenchymal stem cell-derived miR-183-5P targeting FOXO1.

The homing rate of transplanted mesenchymal stem cells (BMSCs) after acute myocardial infarction (AMI) is generally low, with only 0%-6% of the number of transplanted stem cells distributed to the heart; therefore, this study will investigate the therapeutic effects and mechanisms of miR-183-5p-modified BMSCs cells on myocardial ischemia and hypoxia caused by AMI. In this experiment, After first establishing the BMSCs ischemic-hypoxic injury model, the rats were divided into healthy group, model group, BMSCs group and BMSCs+ miR-183-5P group, where the healthy group was taken to normal culture, the model group caused myocardial ischemic-hypoxic damage, the BMSCs group underwent BMSCs stem cell transplantation on the basis of the model group, and the BMSCs+ miR-183-5P group was group was cultured with BMSCs-derived miR-183-5P on the basis of the model group. Myocardial tissue sections of rats in each group were taken for HE staining and histopathological changes were observed by light microscopy. The proliferation, apoptosis and migration ability of the cells were detected by CCK-8 method, flow cytometry and Transwell transfer method. The target gene of miR-183-5P was predicted using bioinformatics software, and the binding of miR-183-5P to FOXO1 was investigated. The expression of FOXO1 was analysed using qRT-PCR and protein blotting techniques. The qRT-PCR results showed that the expression of miR-183-5P was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The value-added ability and the migration capacity of BMSCs in the BMSCs group and BMSCs+ miR-183-5P group were increased compared with the model group, and the BMSCs+ miR-183-5P group BMSCs had the highest proliferation capacity and the migration capacity(P<0.05). In contrast, the apoptotic capacity of BMSCs was significantly reduced in the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the apoptotic capacity of BMSCs was lowest in the BMSCs+ miR-183-5P group (P<0.05). The bioinformatics software RegRNA 2. 0 was used to predict that the specific target gene that may be regulated by miR-183-5P is FOXO1 and confirmed that miR-183-5P does indeed have a targeting relationship with the FOXO1 pathway. After upregulation of miR-183-5P expression, the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The Western blotting showed that the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, especially the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). In conclusion, BMSCs-derived miR-183-5P can target and regulate FOXO1 to increase the proliferation and migration of BMSCs and reduce their apoptosis, and can also reduce myocardial tissue edema and inflammatory response by increasing the expression of FOXO1 mRNA, which can increase the survival rate of BMSCs and provide a clinical basis for BMSCs transplantation.

Formulated chitosan-sodium tripolyphosphate nanoparticles for co-encapsulation of ellagic acid and anti-inflammatory peptide: characterization, stability and anti-inflammatory activity.

BACKGROUND: Chitosan (CS) and tripolyphosphate (TPP) can be combined in the development of a material with synergistic properties and promising potential for the conservation of food products. In this study, ellagic acid (EA) and anti-inflammatory peptide (FPL)-loaded CS nanoparticles (FPL/EA NPs) were prepared using the ionic gelation method and optimal preparation conditions were obtained through a single factor design. RESULTS: The synthesized nanoparticles (NPs) were characterized using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Nanoparticles were spherical, with an average size of 308.33 ± 4.61 nm, a polydispersity index (PDI) of 0.254, a zeta potential of +31.7 ± 0.08 mV, and a high encapsulation capacity (22.16 ± 0.79%). An in vitro release study showed that EA/FPL had a sustainable release from FPL/EA NPs. The stability of the FPL/EA NPs was evaluated for 90 days at 0, 25, and 37 °C. Significant anti-inflammatory activity of FPL/EA NPs was verified by nitric oxide (NO) and tumor necrosis factor-α (TNF-α) reduction. CONCLUSION: These characteristics support the use of CS nanoparticles to encapsulate EA and FPL and improve their bioactivity in food products. © 2023 Society of Chemical Industry.

Lower-dose corticosteroid therapy in severe immune thrombocytopenia during pregnancy: The comparable efficacy and lower incidence of maternal complications.

Background: This study assessed the clinical efficacy of oral prednisone at low dose (LD) versus the previous high-dose (HD) study in patients with severe immune thrombocytopenia during pregnancy and its side effects on maternal and neonatal outcomes. Study design: Pregnant patients with ITP were enrolled in the study (platelet count <30×109/L) between January 2015 and 2019. A total of 43 patients received LD oral prednisone (0.25-0.5 mg/kg) as the initial treatment and were compared retrospectively with the 31 patients in the HD (1 mg/kg) study. The primary clinical endpoint was the response rate, and the secondary endpoint was maternal hemorrhagic events, complications, and neonatal outcomes. Results: In total, 35% of patients responded (15/43) to the LD cortico-therapy, including four patients with a complete response which was no less than HD therapy (35.5%). The bleeding symptoms of 10 (30%) patients were ameliorated after 14 days of LD prednisone treatment. Preeclampsia occurred in three cases (7% of total) of which the incidence was obviously lower than that of the previous study at HD (18%). No stillbirth or miscarriage occurred in the LD group, and neonatal outcomes had no significant differences between the two studies. Conclusion: LD prednisone therapy for severe ITP patients during pregnancy had equal efficacy to HD treatment. In addition, the decrease in dosage significantly reduced the incidence of hypertension.

Plastic surgery for giant metastatic endometrioid adenocarcinoma in the abdominal wall: A case report and review of literature.

BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy, but metastasis to the abdominal wall is extremely rare. Therefore, an appropriate treatment approach for large metastatic lesions with infection remains a great challenge. CASE SUMMARY: We report the case of a 65-year-old woman who developed abdominal metastasis of endometrioid adenocarcinoma, as defined by International Obstetrics and Gynecology stage II, in which the lesion was complicated by infection. A right hemicolectomy was performed for colon metastasis in relation to her initial gynecological cancer 3 years ago. When admitted to our department, a complete resection of the giant abdominal wall lesion was performed, and a Bard composite mesh was used to reconstruct the abdominal wall. A local flap was used to close the resultant large defect in the external covering of the abdomen. The patient underwent chemotherapy following cytoreductive surgery. Pathology revealed metastasis of EC, and molecular subtyping showed copy number high of TP53 mutation, implying a poor prognosis. CONCLUSION: When EC patients develop giant abdominal wall metastasis, a plastic surgeon should be included before contemplating resection of tumors.

Prednisone plus IVIg compared with prednisone or IVIg for immune thrombocytopenia in pregnancy: a national retrospective cohort study.

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

Validation of two risk assessment models for venous thromboembolism in patients undergoing gynecologic surgery.

BACKGROUND: According to published guidelines, gynecologic surgical patients should be stratified into different risk level groups to receive prophylaxis for venous thromboembolism (VTE), but the applicability of available risk assessment models (RAMs) in common gynecologic surgical patients remained to be confirmed. We aimed to validate the use of the Caprini RAM and gynecologic Caprini (G-Caprini) RAM for assessing postoperative VTE risk in gynecologic surgical patients. METHODS: The database of a randomized controlled trial (RCT) was used to select patients who underwent gynecologic surgeries for benignant and malignant diseases in five institutions in China between 2011 and 2018. The Caprini RAM version recommended by the American College of Chest Physicians (ACCP) was adopted. Participants were divided into four risk levels based on the Caprini and G-Caprini scores. For each risk level group, the incidence of VTE was calculated. The correlation between VET incidence and risk levels was assessed by Spearman's rank correlation coefficient (RS) value. RESULTS: As a result, 800 patients in the data base were analyzed with an overall VTE incidence of 5.8%. Caprini RAM showed that the percentage of patients at very low risk, low risk, moderate risk, and high risk were 0%, 4.3%, 44.4%, and 51.4%, respectively, and the VTE incidence was 2.9%, 2.3%, and 9.0%, respectively. RS value between the risk stratification and VTE incidence was 0.500 (P=0.667). G-Caprini RAM showed that the percentage of patients at very low risk, low risk, moderate risk, and high risk were 7.8%, 28.0%, 32.0%, and 32.3%, respectively, and the VTE incidence was 0.0%, 2.9%, 2.3%, and 9.0%, respectively. RS value between the risk stratification and VTE incidence was 1.000 (P<0.01). CONCLUSIONS: The G-Caprini RAM was as suitable as the Caprini RAM for VTE risk assessment in gynecologic surgical patients. The gynecologic model has the advantages of ease of use and more accurate identification of low-risk groups.

Contribution of NADPH oxidase to the retention of UVR-induced DNA damage by arsenic.

Arsenic is a naturally occurring element present in food, soil and water and human exposure is associated with increased cancer risk. Arsenic inhibits DNA repair at low, non-cytotoxic concentrations and amplifies the mutagenic and carcinogenic impact of other DNA-damaging agents, such as ultraviolet radiation (UVR). Arsenic exposure leads to oxidation of zinc coordinating cysteine residues, zinc loss and decreased activity of the DNA repair protein poly(ADP)ribose polymerase (PARP)-1. Because arsenic stimulates NADPH oxidase (NOX) activity leading to generation of reactive oxygen species (ROS), the goal of this study was to investigate the role of NOX in arsenic-induced inhibition of PARP activity and retention of DNA damage. NOX involvement in the arsenic response was assessed in vitro and in vivo. Keratinocytes were treated with or without arsenite, solar-simulated UVR, NOX inhibitors and/or isoform specific NOX siRNA. Knockdown or inhibition of NOX decreased arsenite-induced ROS, PARP-1 oxidation and DNA damage retention, while restoring arsenite inhibition of PARP-1 activity. The NOX2 isoform was determined to be the major contributor to arsenite-induced ROS generation and DNA damage retention. In vivo DNA damage was measured by immunohistochemical staining and analysis of dorsal epidermis sections from C57BI/6 and p91phox knockout (NOX2-/-) mice. There was no significant difference in solar-simulated UVR DNA damage as detected by percent PH2AX positive cells within NOX2-/- mice versus control. In contrast, arsenite-dependent retention of UVR-induced DNA damage was markedly reduced. Altogether, the in vitro and in vivo findings indicate that NOX is involved in arsenic enhancement of UVR-induced DNA damage.

Long-Term Effect of Early Post-operative Transcutaneous Electrical Stimulation on Voiding Function After Radical Hysterectomy: A Multicenter, Randomized, Controlled Trial.

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

Cost-effectiveness of paclitaxel, doxorubicin, cyclophosphamide and trastuzumab versus docetaxel, cisplatin and trastuzumab in new adjuvant therapy of breast cancer in china.

BACKGROUND: Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18-20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. METHODS: A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. RESULTS: We identified 41 breast cancer patients at Hangzhou First People's Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. CONCLUSIONS: This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.