Acellular dermal matrix-assisted tissue expansion for giant congenital melanocytic nevi of the extremities and trunk in pediatric patients.

BACKGROUND: Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly employed surgical method. However, the procedure's efficacy is often hindered by anatomical and histological characteristics as well as blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of non-compliance to medical instructions. OBJECT: To explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders. METHODS: All patients involved in this research underwent ADM-assisted tissue expansion in either the extremities or trunk. ADM was fully flattened, securely fixed to the lower pole of the expander, and subsequently attached to the inner surface of the expanding flap. RESULTS: From 2021 to 2023, a total of nine pediatric patients with GCMN underwent the ADM-assisted tissue expansion. All patients achieved the desired expanding volume without experiencing petechiae, ecchymosis, or skin ulceration in the ADM-covered area. The process was well tolerated by all patients, with no reports of itching, pain, allergic reaction, or fever. During the flap transfer, the ADM was observed to be firmly adhered to the expanding flap with discernible capillary network. CONCLUSION: ADM-assisted tissue expansion demonstrates promise in augmenting expansion efficiency and reducing the time needed for surgical intervention in the extremities and trunk, thereby presenting significant clinical value for pediatric patients afflicted with GCMN.

The Pendulum Movement of Orbital Fat and Retro-Orbicularis Oculi Fat: A New Strategy for Correction of Sunken Eyelid Deformity in Revision Upper Blepharoplasty for Asian Patients.

BACKGROUND: With an increasing number of East Asians undergoing blepharoplasty, the number of patients with secondary upper eyelid deformities is increasing. The sunken eyelid deformity is a common deformity after upper blepharoplasty in Asians due to over-resection, retraction, or atrophy of the nasal and central orbital fat pads. Herein, we present a novel procedure, the pendulum movement of orbital fat and retro-orbicularis oculi fat ("POR" technique), for correction of sunken eyelid deformity in secondary Asian blepharoplasty. METHODS: Patients who underwent secondary upper blepharoplasty with the POR technique by the senior author between January 2020 and October 2021 were identified retrospectively. Those with fewer than 6 months of follow-up were excluded. Patient charts and images were reviewed for demographic data, comorbidities, concomitant eyelid deformities, and postoperative complications. Pre- and postoperative aesthetics, including degree of sunken eyelid deformity, were assessed by two independent raters and by self-reported patient satisfaction. RESULTS: Forty-nine consecutive patients were identified, all of whom were female and had grade I or II sunken eyelid deformity. Median follow-up was 8 months. Concomitant deformities included high tarsal crease (N = 31 patients, 63.3%), ptosis (N = 13, 26.5%), and upper eyelid retraction (N = 5, 10.2%). Almost patients had improvement in their eyelid volume, and 95.9% had improvement in their aesthetic rating. Approximately 93.9% of patients were satisfied with the outcome. CONCLUSIONS: The POR technique is an effective technique for correction of sunken eyelid deformity and can be utilized in conjunction with other techniques during secondary blepharoplasty. 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 .

BAP18 acting as a novel peroxisome proliferator-activated receptor α co-regulator contributes to hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a poor prognosis. The therapeutic outcomes of HCC patients are urgently needed to be improved, and predictive biomarkers for the optimal treatment selection remains to be further defined. In the present study, our results showed that BPTF-associated protein of 18 KDa (BAP18) was highly expressed in HCC tissues. In cultured HCC cells, BAP18 regulated a subset of down-stream genes involved in different functions, particularly including peroxisome proliferator-activated receptor (PPAR) pathway and lipid metabolism. Furthermore, BAP18 co-activated PPARα-mediated transactivation and facilitated the recruitment of nucleosome acetyltransferase of H4 (NuA4)/tat interacting protein 60 (TIP60) complex, thereby increasing histone H4 acetylation on stearoyl-CoA desaturase 1 (SCD1) loci. In addition, BAP18 promoted HCC cell proliferation, increased intracellular lipid levels and enhanced cell survival under the metabolic stress conditions, such as glucose limitation or tyrosine kinase inhibitors (TKIs) treatment. Importantly, higher BAP18 expression was positively correlated with the postoperative recurrence and the poor disease-free survival in clinical patients receiving sorafenib treatment. Altogether, we discovered that BAP18 plays an oncogenic role in the survival and proliferation of HCC cells, and BAP18 may serve as a predictive biomarker for adjunct TKIs treatment in patients with HCC, and further facilitate the precise treatment.

Activation of ALOX12 by a multi-organelle-orienting photosensitizer drives ACSL4-independent cell ferroptosis.

Ferroptosis is a recently-defined tumor suppression mechanism, but the sensitivity of many tumorigenic cells to ferroptosis is limited by their deficient expression of acyl-CoA synthetase long-chain family member 4 (ACSL4). Here, we report the discovery of a photosensitizer, namely TPCI, which can evoke ACSL4-independent ferroptosis of cancer cells in photodynamic therapy. Through co-localization with 12-lipoxygenase (ALOX12) in multiple subcellular organelles, TPCI activates ALOX12 to generate lipid reactive oxygen species in large quantity and trigger cell ferroptosis. Intriguingly, confining TPCI exclusively in lysosomes switches the cell death from ferroptosis to apoptosis. More strikingly, the ferroptosis mediated by TPCI-induced ALOX12 activation does not require the participation of ACSL4. Therefore, our study identifies TPCI as the first ALOX12 activator to induce ferroptosis independent of ACSL4, which renders a viable therapeutic approach on the basis of distinct ferroptosis of cancer cells, regardless their ACSL4 expressions.

Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Morphological evaluation is used to select embryos for in vitro fertilisation. However, it does not fully reflect the implantation potential. Preimplantation genetic testing for aneuploidies (PGT-A) can detect embryonic aneuploidy, but biopsy procedure is invasive. Currently, a non-invasive PGT (ni-PGT) approach using spent medium is being evaluated. However, the clinical benefit of ni-PGT has not been clearly demonstrated. A multicentre randomised trial is needed to verify whether ni-PGT can be an new effective tool for evaluating embryos. METHODS AND ANALYSIS: Overall, 1148 couples aged 35~42 (women) receiving in vitro fertilization-intracytoplasmic sperm injection are planned to be enrolled. Couples will be digitally randomised to (1) ni-PGT and (2) conventional morphology groups at a 1:1 treatment ratio. The primary outcome will be the ongoing pregnancy rate related to the first transfer cycle within 6 months after oocyte retrieval. ETHICS AND DISSEMINATION: The study protocol is approved by the Ethics Committee of Peking University Third Hospital and the participating hospitals. The results will be disseminated through international conferences and scientific journals. TRIAL REGISTRATION NUMBER: NCT04339166.

A Potential Link Between Polycystic Ovary Syndrome and Asthma: a Meta-Analysis.

While there exists some evidence indicating a higher prevalence of asthma in polycystic ovary syndrome (PCOS) patients, whether PCOS is an independent risk factor for asthma remains debatable. In this report, a systematic review and meta-analysis were performed to assess the association between PCOS and asthma. Using of the terms "PCOS," "polycystic ovary syndrome," "polycystic ovarian syndrome," "Stein Leventhal Syndrome," "asthma," and "wheezing," PubMed, Embase, Web of Science, Scopus, Cochrane Trial Register, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for studies published from their inceptions to February 2021. The data were extracted and a meta-analysis was conducted under the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A random-effects model was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI). A total of 6 articles involving 26,876 PCOS women and 156,143 healthy controls were included in this survey. Our results indicate that PCOS patients showed an increased risk of asthma (OR = 1.75, 95% CI = 1.40-2.19, I2 = 91.2%, P = 0.000, random-effects model). No statistically significant differences were obtained when these data were stratified by region, diagnostic criteria for asthma, and study design. PCOS is associated with a higher risk of asthma, a relationship which is independent of region, diagnostic criteria for bronchitis, and study design.

Gene Signatures and Prognostic Values of N6-Methyladenosine Related Genes in Ovarian Cancer.

N6-Methyladenosine (m6A) is one of the most prominent modification regulating RNA processing and metabolism. Increasing studies have illuminated the vital role of m6A methylation in carcinogenesis. However, little is known about the interaction between m6A-related genes and survival of ovarian cancer (OC) patients. The purpose of this study was to obtain more reliable m6A-related genes that could be used as prognostic markers of OC using bioinformatics analysis performed on the RNA-seq data of OC. Gene expression datasets of all m6A-related genes as well as corresponding clinical data were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. We detected differential expressed m6A-related candidate genes as well as their relationship and interaction. m6A RNA methylation regulator ALKBH5 and 35 m6A-related genes are dysregulated in OC. A gene set that could be used as a potential independent prognostic risk feature was further screened including NEBL, PDGFRA, WDR91, and ZBTB4. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. We applied consensus clustering analysis on the expression of the four prognostic genes and obtained four OC subgroups TM1-TM4. There were significant differences in age, stage and grade among the subgroups, and the overall survival (OS) as well as Disease-free survival (DFS) of TM2 group were shorter than those of the other three groups. Further GO and KEGG enrichment analysis indicated that these differential genes were closely related to biological processes and key signaling pathways involved in OC. In summary, our study has indicated that m6A-related genes are key factors in the progression of OC and have potential effects on the prognostic stratification of OC and the development of treatment strategies.

Impact of human adipose tissue-derived stem cells on dermatofibrosarcoma protuberans cells in an indirect co-culture: an in vitro study.

BACKGROUND: Autologous adipose tissue transfer may be performed for aesthetic needs following the resection of dermatofibrosarcoma protuberans (DFSP), the most common cutaneous soft tissue sarcoma, excluding Kaposi sarcoma. The regenerative effectiveness of cell-assisted lipotransfer is dependent on the presence of adipose tissue-derived stem cells (ADSCs). This is the first study to evaluate the potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of DFSP cells. METHODS: Primary DFSP cells were indirectly co-cultured with ADSCs in a conditioned medium or in a Transwell system. The impact was analyzed by assessing proliferation, migration, invasion, angiogenesis, and tumor-associated genes and proteins. Results of these assays were compared between co-culture and mono-culture conditions. RESULTS: Our experimental results showed that ADSCs were able to promote proliferation, migration, invasion, and angiogenesis of DFSP cells; this was accompanied by a significant increase in the expression levels of beta-type platelet-derived growth factor receptor, collagen type I alpha 1 chain, vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor. CONCLUSIONS: The current report clearly demonstrates that ADSCs can enhance different malignant properties of DFSP cells in vitro, which should not be neglected when considering the clinical use of human ADSCs and its related derivatives in skin regenerative therapies.

Bioadhesive metal-phenolic nanoparticles for enhanced NIR imaging-guided locoregional photothermal/antiangiogenic therapy.

Locoregional drug delivery has emerged as a promising solution to the problems associated with intravenously administered antitumor agents, such as systemic toxicity and insufficient drug accumulation at tumor sites. Herein, we have developed an adhesive nanoparticle (NP)-based drug delivery system, using natural bioadhesive tannic acid (TA) and metal ions (Fe3+), for locoregional photothermal and antiangiogenic synergistic cancer therapy. In this study, a new near-infrared (NIR) photothermal agent indocyanine green (IR820) and an antiangiogenic agent sorafenib (SRF) were co-encapsulated in a TA-Fe complex (SIF@TA-Fe). The SIF@TA-Fe NPs exhibited super adhesion, antiangiogenesis, and efficient cellular uptake. Moreover, SIF@TA-Fe NPs showed a synergistic antitumor effect in vivo, including high tumor inhibition rate, excellent survival extension, and low risk of recurrence, resulting from the prolonged retention of the NPs in the tumor. Thus, this adhesive SIF@TA-Fe NP-based therapeutic system provides a promising approach for locoregional drug delivery of combined cancer therapy.

16S rDNA Full-Length Assembly Sequencing Technology Analysis of Intestinal Microbiome in Polycystic Ovary Syndrome.

Objective: To study the characteristics and relationship of the gut microbiota in patients with polycystic ovary syndrome (PCOS). Method: We recruited 45 patients with PCOS and 37 healthy women from the Reproductive Department of Shengjing Hospital. We recorded their clinical indexes, and sequenced their fecal samples by 16S rDNA full-length assembly sequencing technology (16S-FAST). Result: We found decreased α diversity and different abundances of a series of microbial species in patients with PCOS compared to healthy controls. We found LH and AMH were significantly increased in PCOS with Prevotella enterotype when compared to control women with Prevotella enterotype, while glucose and lipid metabolism level remained no significant difference, and situations were opposite in PCOS and control women with Bacteroides enterotype. Ruminococcus gnavus, Prevotella stercorea, Dialister succinatiphilus and Bacteroides fragilis were more abundant while Christensenellaceae spp. were less abundant in the PCOS group. P. stercorea was significantly more prevalent in PCOS-not insulin resistance (NIR) compared to control-NIR and PCOS-not overweight (NOW) patient groups compared to control-NOW groups. Kyoto Encyclopedia Genes and Genomes reflecting pathways related to lipopolysaccharide biosynthesis were more abundant in the PCOS group. Conclusion: Our study found gut microbiota that had different abundance in patients with PCOS compared to healthy controls. An intimate relationship was shown between the gut microbiota and pathological changes in PCOS. We suggest the gut microbiota should be taken into consideration in the treatment of symptoms of PCOS via drugs and diet.

The function of BAP18 on modulation of androgen receptor action in luteinized granulosa cells from normal weight women with and without PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. In this study, BPTF associated protein of 18 kDa (BAP18) is decreased in luteinized granulosa cells (GCs) from PCOS women. BAP18 depletion significantly decreases CYP19A1 expression levels, leading to an abrogation in transfer capacity of androgen to estrogen in GCs. Also, BAP18 knockdown delays cell cycle G1 to S phase transition and induces cell apoptosis to decrease GCs proliferation. We also provide evidence showing BAP18 interacts with androgen receptor (AR) and enhances AR-mediated transactivation in GCs. Results indicate that AR or BAP18 recruits to androgen response elements (AREs) of CYP19A1 and FSHR, which are putative AR-induced genes in GCs. BAP18 interacts with Sp1 transcription factor and co-recruits to the promoter region of AR gene, resulting in AR transactivation in GCs. Taken together, these data provide new insights on the pathophysiology of PCOS.

Conditional deletion of Wntless in granulosa cells causes impaired corpora lutea formation and subfertility.

WNT proteins are widely expressed in the murine ovaries. WNTLESS is a regulator essential for all WNTs secretion. However, the complexity and overlapping expression of WNT signaling cascades have prevented researchers from elucidating their function in the ovary. Therefore, to determine the overall effect of WNT on ovarian development, we depleted the Wntless gene in oocytes and granulosa cells. Our results indicated no apparent defect in fertility in oocyte-specific Wntless knockout mice. However, granulosa cell (GC) specific Wntless deletion mice were subfertile and recurred miscarriages. Further analysis found that GC-specific Wntless knockout mice had noticeably smaller corpus luteum (CL) in the ovaries than control mice, which is consistent with a significant reduction in luteal cell marker gene expression and a noticeable increase in apoptotic gene expression. Also, the deletion of Wntless in GCs led to a significant decrease in ovarian HCGR and ß-Catenin protein levels. In conclusion, Wntless deficient oocytes had no discernible impact on mouse fertility. In contrast, the loss of Wntless in GCs caused subfertility and impaired CL formation due to reduced LHCGR and ß-Catenin protein levels, triggering GC apoptosis.

Near-Infrared AIE Dots with Chemiluminescence for Deep-Tissue Imaging.

Near-infrared (NIR) chemiluminescence (CL) emission is highly favorable for deep-tissue imaging, but chemically conjugated NIR CL emitters with the aggregation-induced emission (AIE) property for biotechnology are seldom reported. Herein, an AIE-active NIR CL emitter, TBL, is synthesized by conjugating luminol unit with electron-accepting benzothiadiazole and an electron-donating triphenylamine, and subsequently TBL dots are prepared by using F127 as the surfactant. The CL emission of TBL dots can last continuously for over 60 min and can be employed for quantitative (in vitro) and qualitative (in vivo) detection of 1 O2 . Strikingly, the NIR CL emission can penetrate through tissues with a total thickness of over 3 cm, exhibiting significantly better performance than NIR fluorescence emission and blue CL emission. Moreover, the successful differentiation of tumor and normal tissues by TBL-based CL imaging in vivo also paves the way for CL-guided cancer diagnosis and surgery.

An effective method for trophectoderm biopsy using mechanical blunt dissection: a step-by-step demonstration.

OBJECTIVE: To present an effective approach to trophectoderm biopsy for blastocysts of different stages and characteristics by mechanical blunt dissection (MBD). DESIGN: Stepwise demonstration with still pictures and operational video clips to explain tips and tricks for trophectoderm biopsy. (This demonstration was approved by the Reproductive Study Ethics Committee at Shengjing Hospital of China Medical University.) SETTING: In vitro fertilization laboratory. PATIENT(S): Patients who underwent preimplantation genetic testing. INTERVENTION(S): The illustrated techniques of blastocyst trophectoderm biopsy using micromanipulation methods include artificial shrinkage, zona pellucida drilling, injecting media from the drilling, aspiration of trophectoderm cells into the biopsy pipette (outer diameter 27 µm for fully expanded blastocysts and peanut-shaped hatching blastocysts; outer diameter 20 µm for 8-shaped hatching and hatched blastocysts), detachment of the trophectoderm cells by laser pulse combined with MBD (performed using the rims of the biopsy and holding pipettes), and release of the biopsy fragment. MAIN OUTCOME MEASURE(S): Successful biopsy rate and survival after warming. RESULT(S): Our biopsy strategy does not involve assisted hatching on day-3 or day-4 embryos, which can leave the embryo undisturbed in culture up to the expanded blastocyst stage. Notably, this approach demonstrates several noteworthy advantages for sampling blastocysts of different stages and characteristics, and it maintains a desirable successful biopsy rate (95.4%, n = 1,872) and survival rate after warming (100%, n = 440). The MBD method may reduce thermal damage because fewer laser pulses are used, compared with the traditional laser-only biopsy techniques. For noncollapsed blastocysts after artificial shrinkage, the strategy of injecting medium from the zona pellucida drilling helps to separate the trophectoderm cells from the zona pellucida, thus facilitating the biopsy procedure. For peanut-shaped hatching blastocysts, this approach could provide better control over the aspiration of trophectoderm cells into the biopsy pipette. Especially if the inner cell mass is herniating from the zona pellucida, the trophectoderm biopsy can be performed away from the inner cell mass to avoid damaging it. In addition, the MBD approach combined with the biopsy pipette (outer diameter 20 µm) can effectively control the target number of trophectoderm cells, thus simplifying the process of obtaining a biopsy from a hatched blastocyst. CONCLUSION(S): Our biopsy approach demonstrates several noteworthy advantages. Considering its benefits and the simplicity of its execution, this systematic biopsy method for blastocysts of different stages and characteristic can be widely applied.

Platinum-AIEgen coordination complex for imaging-guided annihilation of cisplatin-resistant cancer cells.

We report the synthesis and comprehensive characterization of a new platinum-AIEgen coordination complex. Possessing a high 1O2 quantum yield of 0.75 in water, the complex efficiently kills cisplatin-resistant cancer cells under mild white light irradiation. Its strong fluorescence upon binding with proteins also enables direct visualization of its intracellular distribution.

Treatment Strategy for Radical Resection of Giant Neurofibroma.

The management of giant neurofibroma is a challenge for clinical surgeons. Abundant malformed vessels exist in the tumor, and life-threatening hemorrhage can occur during operation. Moreover, repairing huge defects after radical resection is challenging. Hence, subtotal resection and debulking are more frequently performed than total resection. Although subtotal resection or debulking may reduce morbidity, it inevitably leads to a high rate of recurrence. In addition, subtotal resection or debulking does not decrease surgical risk; on the contrary, when operating on the tumor body, the rate of hemorrhage is much higher in case of subtotal resection and debulking than in radical resection. In this study, 9 patients with giant neurofibroma were retrospectively reviewed. The tumor size ranged from 12 × 9 cm to 60 × 70 cm. Preoperative angiography and magnetic resonance imaging scanning are performed to clarify the tumor features. All patients underwent radical resection, and in-operation blood loss ranged from 300 to 2600 mL. The resection defects were repaired by anterolateral thigh free flap in 2 patients and skin grafts in 7 patients. Partial skin necrosis occurred in 4 patients, and the necrosis area can be repaired with adjacent survived skin by changing the dressing several times. No tumor recurrence was recorded during routine follow-up (range, 12-39 months). The treatment strategy for radical resection of giant neurofibroma proves effective, and the technique of reusing the skin provides sufficient material for covering a large defect without the morbidity associated with a new donor. Thus, tumor removal and wound repair can be accomplished in one stage.

Fructose levels are elevated in women with polycystic ovary syndrome with obesity and hyperinsulinemia.

STUDY QUESTION: Are fructose levels altered in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Elevated serum fructose levels are associated with PCOS in Chinese Han women with overweight/obesity and hyperinsulinemia, and fructose levels are higher in follicular fluids from PCOS patients than from control subjects. WHAT IS KNOWN ALREADY: Both fructose levels and PCOS are closely linked to obesity and insulin resistance. However, the relationship between fructose and PCOS remains largely unknown. STUDY DESIGN, SIZE, DURATION: A total of 157 Chinese Han women (67 controls and 90 PCOS patients) were recruited at Shengjing Hospital of China Medical University. To systematically study the relationship between serum fructose levels and PCOS, the study population of control subjects and PCOS patients was divided into overweight/obese and lean subgroups, and hyper-fasting serum insulin (FSI) and normal-FSI subgroups, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fructose levels were measured in serum samples collected from 80 patients with PCOS (32 lean, 48 overweight/obese) and 59 control subjects (27 lean, 32 overweight/obese) and in follicular fluid samples collected from mature follicles (17-22 mm) and matched immature follicles (8-13 mm) from 10 patients with PCOS and 8 control subjects. MAIN RESULTS AND THE ROLE OF CHANCE: Serum fructose levels were increased in overweight/obese and hyper-FSI PCOS patients compared with the control subjects. Fructose had an area under the curve (AUC) of 79.7% at a cutoff value of 10.13 pmol/µl, with a sensitivity of 91.7% and a specificity of 59.3% for the prediction of PCOS in overweight/obese patients. In the hyper-FSI group, fructose had an AUC of 72% at a cutoff value of 10.49 pmol/µl, with a sensitivity of 71.1% and a specificity of 64.4% for the prediction of PCOS. There were no differences between fructose, total testosterone, free testosterone or dehydroepiandrosterone sulfate levels with respect to the reliability of predicting PCOS in the overweight/obese or hyper-FSI groups using the method outlined by Hanley and McNeil. Notably, the combination of fructose and total testosterone levels resulted in the highest AUC of 86.0% and high sensitivity (85.4%) and specificity (83.1%) for the prediction of PCOS in overweight/obese patients. The positive predictive value (PPV) and negative predictive value (NPV) were 80.4 and 87.5%, respectively. Similarly, the combination of fructose and total testosterone levels also resulted in a high AUC of 80.2% and moderate sensitivity (73.3%) and high specificity (84.7%) for the prediction of PCOS in hyper-FSI patients. The PPV and NPV were 78.6 and 80.6%, respectively. Furthermore, fructose levels were significantly higher in follicular fluids from PCOS patients than from control subjects, regardless of whether the follicles were mature or immature. LIMITATIONS, REASONS FOR CAUTION: It remains unclear whether fructose levels contribute directly to follicular development and the pathogenesis of PCOS or are merely a biomarker of these processes. WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study, together with our previous study, show that monosaccharide status may be a novel marker for PCOS, highlighting the importance of further investigation into the role of monosaccharides, especially fructose, in the pathogenesis of PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (No. 81671423 and No. 81402130), the National Key Research and Development Program of China (No. 2018YFC1003100), Liaoning Provincial Key Research and Development Program (No. 2018225090), the Fok Ying Tung Education Foundation (No. 151039), Distinguished Talent Program of Shengjing Hospital (No. ME76) and Distinguished Teacher Program of China Medical University (No. QGZ2018079). No competing interests were declared.

Paclitaxel-Potentiated Photodynamic Theranostics for Synergistic Tumor Ablation and Precise Anticancer Efficacy Monitoring.

Photodynamic theranostics that allows for concurrent photodynamic therapy (PDT) and precise therapeutic response report has emerged as an intriguing direction in the development of precision medicine. An ultra-efficient photodynamic theranostics platform was developed here based on combining and potentiating a theranostic photosensitizer, TPCI, with other therapies for synergistic anticancer effect and synchronous self-reporting of therapeutic response. In this study, TPCI and a chemotherapy agent paclitaxel (PTX) were co-encapsulated in liposomes, which exhibited a superb synergistic anticancer effect against a series of tumor cell lines. The potency of both drugs had been boosted for up to 30-fold compared with sole PDT or chemotherapy. More strikingly, the released TPCI lighted up the nuclei of dead cells, triggered either by PDT or chemotherapy, through binding with the chromatin and activating its aggregation-induced emission, therefore self-reporting the anticancer effect of the combined therapy in real time. The in vivo study using a mouse model bearing PC3 prostate tumor cells demonstrated the effective ablation of tumors with initial sizes of 200 mm3 and the precise early tumor response monitoring by TPCI/PTX@Lipo. This PTX-potentiated photodynamic theranostics strategy herein represented a new prototype of self-reporting nanomedicine for precise tumor therapy.

S-shaped wound closure following the excision of 2 adjacent pigmented nevi.

BACKGROUND: The main goal of excision of a pigmented nevus is to achieve an esthetically pleasing result. A single nevus can be removed by simple excision, whereas S-shaped suture can be used for the excision of 2 adjacent nevi. However, the choice of suturing method is based on the experience of the dermatologic surgeon, as there is no uniform standard for suture following the excision of 2 adjacent nevi. The aim of the present study was to determine whether S-shaped wound closure is appropriate for the excision of 2 adjacent nevi. METHODS: The outcomes of 21 patients who underwent simultaneous resection of 2 adjacent nevi were retrospectively reviewed. Of these patients, 17 chose S-shaped suture and 4 chose direct suture. Patients were followed-up for more than 6 months to review their postoperative scars. Differences between the 2 methods were compared based on the patient and observer scar assessment scale. Diameters and the proportional relationship between the 2 nevi were analyzed. RESULTS: Patients who underwent S-shaped wound closure surgery were more satisfied compared to those who had direct suturing (P<0.05); the nevus diameter-to-spacing diameter ratio was 0.68±0.35:1:0.99±0.56 in the S-shaped wound closure group. CONCLUSIONS: S-shaped wound closure following the excision of 2 adjacent nevi resulted in better patient satisfaction than the conventional direct suturing method.

Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy.

One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically "cold" tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn "cold" tumors "hot." Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating "cold" tumors.