Methylene Blue Combined with Ropivacaine for Intercostal Nerve Block After Autologous Costal Cartilage Removal in Juvenile Patients.

OBJECTIVES: Autologous costal cartilage is commonly used as a graft material in plastic surgery. However, after autologous costal cartilage removal, the pain at the surgical site is particularly strong. We conducted this controlled clinical study to verify the efficacy of methylene blue (MB) in intercostal nerve block after autologous costal cartilage removal and to provide a reference for the application of MB in postoperative analgesia after autologous costal cartilage removal. METHODS: In this study, 90 adolescent patients with congenital microtia who underwent autologous rib cartilage graft for auricular reconstruction were randomly allocated to one of three groups (Group A: intercostal nerve block was performed with 0.75% ropivacaine; Group B: intercostal nerve block was performed with 1% MB; and Group C: intercostal nerve block was performed with 1% MB and 0.75% ropivacaine mixture). Two trained researchers observed and recorded the pain status of the children at 6 hours (T1), 24 hours (T2), 48 hours (T3), and 72 hours (T4) after surgery, respectively. Numerical rating pain scale (NRS) was used for scoring. And adverse reactions such as nausea, vomiting, and skin itching were recorded. RESULTS: In this study, there was no statistical difference in age and gender of patients in Groups A, B, and C (P >0.05). In terms of NRS comparison, 6 hours after operation (T1), Group B > Group A > Group C (P< 0.05); 24 hours after operation (T2), Group B > Group A > Group C (P< 0.05); 48 hours after operation (T3), Group B > Group A > Group C (P< 0.05); 72 hours after operation (T4), Group A > Group B > Group C (P< 0.05). There were no statistically significant differences in postoperative nausea, vomiting, and skin itching among the three groups (P>0.05). CONCLUSION: The analgesic effect of IV self-controlled analgesia combined with ropivacaine is quick, but the maintenance time is short. The analgesic effect of IV self-controlled analgesia combined with MB is slow to onset but long to maintain. The analgesic effect of IV self-controlled analgesia combined with MB and ropivacaine mixture is quick and maintained for a long time. Therefore, in patients after removal of costal cartilage, we recommend the analgesic treatment method of IV self-controlled analgesia combined with MB and ropivacaine mixture. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Special Topic.

Comparison of Pregnancy Outcomes Between Single-Morula Embryo Transfer and Single-Blastocyst Transfer in Fresh IVF/ICSI Cycles.

BACKGROUND This study investigated the effectiveness and feasibility of day 4 (D4) morula embryo transfer (ET) in comparison with day 5 (D5) blastocyst ET, with regards to their clinical data, laboratory test results, and pregnancy outcomes. MATERIAL AND METHODS This retrospective cohort study enrolled 1070 patients, including 178 cases in group D4 and 892 cases in group D5. The endpoint was live birth rate after fresh embryo transfer. Furthermore, the clinical outcomes of D4 embryos with different morphology were compared and assigned to 3 groups: in group 1 (n=66) the embryos were compacted but not expanded, in group 2 (n=102) the embryos were compacted and expanded (early blastocyst), and in group 3 (n=10) the embryos were not compacted. RESULTS Groups D4 and D5 had comparable clinical pregnancy rates (53.37% vs. 59.97%) and live birth rates (43.25% vs 50.89%), and there were no significant differences between the 2 groups. In group 3, there was only 1 clinical pregnancy and no live birth. In comparison between group 1 and group 2, the clinical pregnancy rate of group 2 showed an upward trend (48.48% vs 60.78%), but there was no significant difference. There was also no statistically significant difference in the live birth rate between the 2 groups (42.42% vs 49.01%). CONCLUSIONS Transferring of compacted embryos or early blastocysts can result in high clinical pregnancy rates and live birth rates. In addition to the cleavage and blastocyst ET, morula ET may serve as an alternative option for the clinician.

The Efficacy of Drug Injection in the Treatment of Pathological Scar: A Network Meta-analysis.

BACKGROUND: Pathological scars mainly include hyperplastic scars and keloids, and there is no uniform treatment standard for the treatment of pathological scar in clinic now. Drug injection in the treatment of pathological scar is widely used because of its advantages of less trauma and simple operation. Therefore, we used a network meta-analysis to compare the curative effect of four kinds of drugs which are commonly used in the treatment of pathological scar such as botulinum toxin type A, corticosteroids (including diprospan and triamcinolone acetonide (TAC)), verapamil and 5-fluorouracil (5-FU), systematically. It is hoped that our study will provide evidence for the choice of drugs in the treatment of pathological scar by injection. METHODS: Relevant articles from Wanfang, VIP, CNKI, PubMed, Cochrane Library and Embase databases were extracted by us. They were included into a network meta-analysis to compare the four kinds of drugs which are commonly used in the treatment of pathological scar. RESULTS: The network meta-analysis included a total of 1513 patients from 23 studies. Through meta-analysis, we found that the efficacy of botulinum toxin type A combined with corticosteroid drugs was best in the treatment of pathological scar by injection. There was no significant difference between botulinum toxin type A, corticosteroids combined with 5 Fu, verapamil and 5-FU. The efficacy of corticosteroids combined with 5-FU was better than that of corticosteroids alone and verapamil alone, but there was no significant difference between them and 5-FU. Further, the order of efficacy predicted by the SUCRA curve was as follows: botulinum toxin type A combined with corticosteroids > corticosteroids combined with 5-FU > botulinum toxin type A > corticosteroids > 5-FU > verapamil. Moreover, no publication bias was found in the funnel diagram. CONCLUSION: In the injection treatment of pathological scar, we recommend the combined injection of two drugs, especially botulinum toxin type A combined with corticosteroids. The effective treatment of botulinum toxin type A combined with corticosteroids in the treatment of pathological scar is as follows: Patients were treated once monthly with intralesional injection of TAC (0.1 ml/cm3) mixed with botulinum toxin type A (2.5 IU/cm3) for a total of 3 treatments. However, there are still limitations in this network meta-analysis, and its conclusion still needs to be further confirmed by more randomized controlled trials. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Duplications involving the long range HMX1 enhancer are associated with human isolated bilateral concha-type microtia.

BACKGROUND: Microtia is a congenital anomaly of ear that ranges in severity from mild structural abnormalities to complete absence of the outer ears. Concha-type microtia is considered to be a mild form. The H6 family homeobox 1 transcription factor gene (HMX1) plays an important role in craniofacial structures development. Copy number variations (CNVs) of a downstream evolutionarily conserved enhancer region (ECR) of Hmx1 associated with ear and eye abnormalities have been reported in different animals, but not yet in human. To date, no genetic defects responsible for isolated human microtia has been reported except for mutations in HOXA2. Here we recruited five Chinese families with isolated bilateral concha-type microtia, and attempt to identify the underlying genetic causes. METHODS: Single Nucleotide polymorphism (SNP) array was performed to map the disease locus and detect CNVs on a genome scale primarily in the largest family (F1). Whole genome sequencing was performed to screen all SNVs and CNVs in the candidate disease locus. Array comparative genomic hybridization (aCGH) was then performed to detect CNVs in the other four families, F2-F5. Quantitative real-time polymerase chain reaction (qPCR) was used to validate and determine the extent of identified CNVs containing HMX1-ECR region. Precise breakpoints in F1 and F2 were identified by gap-PCR and sanger sequencing. Dual-luciferase assays were used to detect the enhancer function. qPCR assays were also used to detect HMX1-ECR CNVs in 61 patients with other types mictrotia. RESULTS: Linkage and haplotype analysis in F1 mapped the disease locus to a 1.9 Mb interval on 4p16.1 containing HMX1 and its downstream ECR region. Whole genome sequencing detected no potential pathogenic SNVs in coding regions of HMX1 or other genes within the candidate disease locus, but it detected a 94.6 Kb duplication in an intergenic region between HMX1 and CPZ. aCGH and qPCRs also revealed co-segregated duplications in intergenic region downstream of HMX1 in the other four families. The 21.8 Kb minimal overlapping region encompassing the core sequences consensus with mouse ECR of Hmx1. Luciferase assays confirmed the enhancer function in human sequences, and proved that HOXA2 could increase its enhancer activity. No CNVs were detected in HMX1-ECR regions in 61 patients with other type of microtia. CONCLUSION: Duplications involving long range HMX1 enhancers are associated with human isolated bilateral concha-type microtia. We add to evidences in human that copy number variations in HMX1-ECR associates with ear malformations, as in other species. This study also provides an additional example of functional conserved non-coding elements (CNEs) in humans.

Understanding of COVID-19 based on current evidence.

Since December 2019, a series of unexplained pneumonia cases have been reported in Wuhan, China. On 12 January 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019-nCoV). On 11 February 2020, the WHO officially named the disease caused by the 2019-nCoV as coronavirus disease (COVID-19). The COVID-19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID-19 in the hope of providing a reference for future studies and help for the prevention and control of the COVID-19 epidemic.

CD-sACE2 inclusion compounds: An effective treatment for coronavirus disease 2019 (COVID-19).

Coronaviruses are common human viruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV), the middle east respiratory syndrome coronavirus and the SARS-CoV-2. Coronaviruses mainly bind to transmembrane receptor proteins on the human cell membrane through spike proteins (S-proteins), thus releasing the RNA of the virus into the interior of the host cell to cause an infection. In this article, we discuss the mechanism and production of cyclodextrin-soluble angiotensin-converting enzyme 2 (CD-sACE2) inclusion compounds in the treatment of SARS-CoV-2 infections by blocking S-proteins. On the basis of the current research evidence, we believe that CD-sACE2 inclusion compounds have the potential to treat COVID-19. We hope that our article can provide a theoretical basis for later experiments.

Expression patterns of C1ql4 and its cell-adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis.

C1q-like 4 (C1QL4), a novel member of the C1q- and TNF-related protein family, was found to be highly expressed in rodent and human testis. However, the localization, developmental, and hormonally regulated expression and biologic function of C1ql4 in the testis have not been investigated. Here, we demonstrated that C1ql4 mRNA and protein levels in murine testes gradually increased from the postnatal period to the adult stage and were up-regulated by LH in vivo. In situ hybridization demonstrated that the distribution and expression levels of C1ql4 mRNA varied at different developmental stages, although C1ql4 mRNA was detected in the seminiferous tubule and interstitial Leydig cells. Recombinant C1QL4 did not affect cell proliferation but did increase testosterone production in TM3 Leydig cells, as well as in cultured seminiferous tubules. C1QL4-induced testosterone secretion in Leydig cells was accompanied by increased expression of steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes. During this process, the c-Raf/extracellular signal-regulated protein kinase kinases 1 and 2/ERK1/2/mitogen- and stress-activated protein kinase-1 and cAMP/PKA/cAMP-responsive element binding protein signaling cascades were activated by C1QL4. The cell-adhesion GPCR brain-specific angiogenesis inhibitor 3 (BAI3), a putative receptor of C1QL4, was detected in the seminiferous tubule and interstitial Leydig cells during testicular development. Knockdown of Bai3 expression in Leydig cells led to a reduction in Star expression, accompanied by increases in phosphorylation of ERK1/2 and intercellular cAMP levels. However, C1QL4-induced StAR expression was not completely suppressed in the Bai3-deficient Leydig cells, and phosphorylation of ERK1/2 and intercellular cAMP levels were not significantly changed before and after C1QL4 stimulation. Our results suggested that although BAI3 played a role in C1QL4-induced steroidogenesis, there was an unidentified receptor that mediated C1QL4-activated testosterone secretion in Leydig cells through phosphorylation of ERK1/2 and up-regulation of intracellular cAMP levels. Taken together, our results showed, for the first time to our knowledge, that C1QL4 served as a novel acute regulator of testosterone secretion, and BAI3 functioned as a new receptor that is involved in steroidogenesis in Leydig cells. BAI3-independent ERK1/2 activation and cAMP activation mediated C1QL4-induced testosterone secretion. This study expanded the reproductive roles and mechanisms of C1QL4 and BAI3 signaling pathways.-Tan, A., Ke, S., Chen, Y., Chen, L., Lu, X., Ding, F., Yang, L., Tang, Y., Yu, Y. Expression patterns of C1ql4 and its cell-adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis.

Assisted oocyte activation with calcium ionophore 44 hours after intracytoplasmic sperm injection resulting in successful pregnancy.

Assisted Oocyte Activation (AOA) with Calcium Ionophore, is possible to manually activate the oocytes and cure globozoospermia, thus leading to successful pregnancy in 1 h after ICSI. But in this case, we report a case that 44 h after ICSI, the arrest zygotes assisted oocyte activation with calcium ionophore, obtained clinical pregnancy and live birth. Accordingly, AOA may provide us with an immediate treatment for embryonic arrest in the future.

Review of Preferential Suspicious Genes in Microtia Patients Through Various Approaches.

Recently, an increasing trend of the birth prevalence of anotia/microtia is observed in China, contributed by changes of social environment and lifestyle. There seems to be no major breakthroughs in exact pathogenesis of microtia, though the research results related to molecular genetics unceasingly appear. In this review, the authors focus on the results of various research methods which the authors regard as the preferential suspicious gene pool to facilitate the exploration of the pathogenic genes of microtia, knowing that the mechanism of microtia is very complicated. The advantages and limitations of these various approaches will also be systematically delineated. The authors believe that this review will give a deep insight in the genetic research of microtia and help plastic surgeons manage congenital microtia more effectively.

An epididymis-specific secretory protein Clpsl2 critically regulates sperm motility, acrosomal integrity, and male fertility.

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. Here we report that Clpsl2, a novel colipase homology, is exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2 was secreted into the lumen and covered the acrosome region and principal piece of spermatozoa tail. And during epididymal transit, the binding rate between Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved amino acids in pancreatic Clps that interacting with lipase, correspondingly, the recombinant Clpsl2 protein did not possess the Clps function such as promoting the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown expression of Clpsl2 by lentivirus-mediated RNAi in vivo caused an attenuation of spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda spermatozoa number, and subfertility. This study identified a novel and conserved molecule, Clpsl2, was specifically expressed in epididymis and involved in the regulation of spermatozoa motility, acrosomal integrity, and male fertility.

C1QTNF3 in the murine ovary and its function in folliculogenesis.

C1q/tumor necrosis factor-related protein 3 (C1QTNF3) is a novel adipokine with modulating effects on metabolism, inflammation and the cardiovascular system. C1QTNF3 expression levels in the sera and omental adipose tissues of women with PCOS are low compared to control subjects. However, the expression and function of C1QTNF3 in the ovary has not previously been examined. Here, we assessed the expression patterns of C1qtnf3 in the ovary and explored its role in folliculogenesis. The C1qtnf3 transcript abundance was higher in large follicles than in small follicles and was under the influence of gonadotropin. C1QTNF3 was detected mainly in the granulosa cells and oocytes of growing follicles and modestly in the granulosa cells of atretic follicles and in luteal cells. Excess androgen significantly decreased C1QTNF3 expression in the ovaries in vivo and in granulosa cells in vitro Recombinant C1QTNF3 protein accelerated the weight gain of ovarian explants and the growth of preantral follicles induced by follicle stimulating hormone (FSH) in vitro The stimulatory effect of C1QTNF3 on ovarian growth was accompanied by the initiation of AKT, mTOR, p70S6K and 4EBP1 phosphorylation, an increase in CCND2 expression and a reduction in cleaved CASP3 levels. Moreover, the addition of C1QTNF3 accelerated proliferation and reduced activated CASP3/7 activity in granulosa cells. In vivo, the ovarian intrabursal administration of the C1QTNF3 antibody delayed gonadotropin-induced antral follicle development. Taken together, our data demonstrate that C1QTNF3 is an intraovarian factor that promotes follicle growth by accelerating proliferation, decelerating apoptosis and promoting AKT/mTOR phosphorylation.

Peri-ovarian adipose tissue contributes to intraovarian control during folliculogenesis in mice.

Peri-ovarian adipose tissue (POAT) is a kind of intra-abdominal white adipose tissue that is present surrounding the ovaries in rodents. Recent studies demonstrated that POAT-deficient mice displayed a phenotype of delayed antral follicular development, for which decreases in serum estrogen, serum FSH and FSHR levels were responsible. However, folliculogenesis is regulated by endocrine signals and also modulated by a number of locally produced intraovarian factors whose acts are both autocrine and paracrine. Here, we used a model of surgical removal of POAT unilaterally and contralateral ovaries as controls, as both were under the same endocrine control, to assess the paracrine effect of the POAT on folliculogenesis. Surgical removal of unilateral POAT resulted in delayed antral follicular development and the increased number of atretic follicles, accompanied by decreased levels of intraovarian adipokines and growth factors, lipid accumulation and steroidogenic enzyme expression. POAT-deficient ovaries displayed compensatory increased expressions of intraovarian genes, such as Vegf and Adpn for angiogenesis, Acc, Fasn, and Gapdh involved in lipogenesis and Fshr in response to FSH stimulation. Furthermore, we demonstrated that removal of POAT promoted follicular apoptosis, caused retention of cytoplasmic YAP and inhibited PTEN-AKT-mTOR activation. These alterations were observed only in the POAT-deficient ovaries but not in the contralateral ovaries (with POAT), which suggests that a paracrine interaction between POAT and ovaries is important for normal folliculogenesis.

Effect of micronutrient supplementation on IVF outcomes: a systematic review of the literature.

There is accumulating evidence on the importance of micronutrients in improving fertility in couples undergoing IVF therapy. Despite this, studies reporting the relevant clinical outcomes of IVF, such as pregnancy and live birth rates, are very scarce. This review aimed to systematically summarize clinical evidence on the effect of micronutrients on primary outcome parameters of IVF treatment. The literature was searched up to February 2017 through Embase and PubMed databases for relevant studies. The quality of eligible studies was assessed with the Downs and Black checklist. A total of five studies qualified for inclusion. These studies reported outcomes on 467 participants administered micronutrient supplements alone or combined with other nutrients as part of IVF therapy. There was significant heterogeneity among the interventions and study designs. However, all the studies reported a positive impact of micronutrient supplementation on clinical outcomes of IVF therapy in terms of pregnancy rate and/or live birth rate. Within the limits of this review, micronutrients appear to influence positive outcomes in couples undergoing fertility treatment. Larger clinical studies are needed to strengthen these findings so that the benefit of micronutrients can be extended to subjects undergoing IVF therapy.

The effect of protein supplement concentration in embryo transfer medium on clinical outcome of IVF/ICSI cycles: a prospective, randomized clinical trial.

The aim of this prospective, randomized clinical trial (RCT) was to evaluate whether the supplemental protein concentration in embryo transfer (ET) medium affects the clinical outcomes in IVF-ET. A total of 750 patients undergoing IVF-ET who met the inclusion criteria were randomly divided into three groups, according to the concentration of synthetic serum substitute (SSS) in ET medium as follows: 10% (Group A), 20% (Group B) and 50% (Group C). The patient characteristics and embryology data were all similar among the groups. The rates of implantation, clinical pregnancy and live birth were compared. Clinical pregnancy (44.61%, 48.79% and 45.49%), multiple pregnancy (24.18%, 28.71% and 25.0%), implantation (28.21%, 30.68% and 29.86%) and live birth (41.67%, 43.96% and 41.70%) rates in the three groups (A, B and C, respectively) showed no significant differences. This RCT demonstrates that supplemental protein concentration in the ET medium does not affect the treatment outcomes in IVF-ET. There was no statistical evidence to support the hypothesis that supplemental protein concentration in the ET medium influences treatment outcomes in IVF-ET.

5,7-Dihydroxy-4'-methoxyisoflavone induces apoptosis by inhibiting the ERK and Akt pathways in human osteosarcoma cells.

Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. In this study we determine the effect of 5,7-dihydroxy-4'-methoxyisoflavone, a phytoestrogen, on proliferation and apoptosis in the human osteosarcoma (OS) cell line U2OS. 5,7-Dihydroxy-4'-methoxyisoflavone dose-dependently inhibited proliferation in U2OS cells, which was accompanied by an increase of early apoptotic cells. However, 5,7-dihydroxy-4'-methoxyisoflavone had little effect on the growth and apoptosis of normal human skin fibroblast (HSF) cells. This may indicate that 5,7-dihydroxy-4'-methoxyisoflavone can selectively inhibit the proliferation of cancerous cells. Meanwhile, 5,7-dihydroxy-4'-methoxyisoflavone decreased the protein levels of phosphorylated ERK and Akt. Inactivation of these pathways was confirmed by upregulation of Bax expression and downregulation of Bcl-2 expression. Phosphorylated Akt protein levels were decreased in HSF cells only at a high concentration (80 µM) of 5,7-dihydroxy-4'-methoxyisoflavone. Together, we suggest that 5,7-dihydroxy-4'-methoxyisoflavone promotes cell death of human OS cells U2OS by induction of apoptosis, which is associated with the inhibition of ERK and Akt signaling. Thus, 5,7-dihydroxy-4'-methoxyisoflavone may have less toxicity compared to normal tissue and could be a potential therapy for OS.

Red Blood Cell Membrane-Coated Nanoparticles Enable Incompatible Blood Transfusions.

Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.

Picropodophyllin inhibits epithelial ovarian cancer cells in vitro and in vivo.

Epithelial ovarian cancer (EOC) is one of the leading causes of gynecological cancer death. Approximately 70% of the patients experience recurrence accompanied by the development of drug resistance 2-3 years after chemotherapy. Picropodophyllin (PPP) is a newly identified insulin-like growth factor-1 receptor (IGF-1R) inhibitor that has been shown to have anticancer properties. In this study, we investigated the effect of PPP on EOC growth in vitro and in vivo. The EOC cell line SKOV-3 was treated with increasing concentrations of PPP or cisplatin, and cell viability and apoptosis were evaluated. To study the effects of PPP on EOC growth, apoptosis, and toxicity in vivo, a BALB/c nude mouse xenograft model was established. Mice were treated with normal saline (controls), PPP, cisplatin, or PPP in combination with cisplatin. In addition, the expression of phosphorylated IGF-1R (pIGF-1R) was examined in vitro and in vivo. PPP induced a dose-dependent decrease in SKOV-3 cell viability in vitro and reduced tumor volume and weight in the in vivo xenograft model. Furthermore, PPP in combination with cisplatin was more effective in inhibiting the growth of SKOV-3 cells and xenografts than either drug alone. PPP-mediated growth inhibition was associated with apoptosis induction in vitro and in vivo. PPP was well tolerated in vivo and exerted its effects with minimal hepatotoxicity and renal toxicity. PPP downregulated the expression of pIGF-1R in vitro and in vivo, an effect that appeared to be associated with its growth inhibitory properties. Our results indicate that PPP may have therapeutic application in the treatment of EOC.

Comparison of frozen-thaw blastocyst transfer strategies in women aged 35-40 years: a retrospective study.

Objective: To compare the effects of five different frozen-thaw embryo transfer (FET) strategies in women aged 35-40 years. Methods: Data from 1,060 patients were divided into five groups according to the number and quality of transferred blastocysts: a high-quality single blastocyst group (group A, n= 303), a high-quality double blastocysts group (group B, n= 176), a high-quality plus poor-quality double blastocysts group (group C, n= 273), a poor-quality double blastocysts group (group D, n= 189), and a poor-quality single blastocyst group (group E, n= 119). Comparative analyses were then performed between groups with regard to primary conditions, pregnancy, and neonatal outcomes. Results: Group A had the lowest twin pregnancy rate (1.97%) and incidence of low-birth-weight infants (3.45%), which were significantly different from groups B, C, and D. In addition, the preterm birth rate (7.89%), neonatal birth weight (3300 g [3000, 3637.5]), and neonatal birth age (39.14 weeks [38.43, 39.61]) in group A were different from those in groups B and C. Double blastocyst transfer (DBT) was associated with a 20.558-fold (Risk Ratio [RR]=20.558, 95% confidence interval [CI], 6.628-63.763) and 3.091-fold (RR=3.091, 95% CI, 1.69-5.653) increased risk of twin pregnancy and preterm delivery in unadjusted analysis, respectively, when compared with single blastocyst transfer (SBT). In the adjusted analysis, we observed similar risk estimates (adjusted RR=26.501, 95% CI, 8.503-82.592; adjusted RR=3.586, 95% CI, 1.899-6.769). Conclusion: Although, high-quality SBT resulted in a lower live birth rate than high-quality DBT, it also significantly reduced the risk of adverse pregnancies, thus resulting in more benefits for both the mother and baby. Collectively, our data indicate that high-quality SBT remains the optimal FET strategy for women aged 35-40 years and warrants further clinical application.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

Doxorubicin Detoxification in Healthy Organs Improves Tolerability to High Drug Doses for Enhanced Antitumor Therapy.

With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.