The Clinical Application of Double Taylor Spatial Frame in Segmental Tibial Fracture.

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.

Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Correction: A non-sacrificial method for the quantification of poly(ethylene glycol) grafting density on gold nanoparticles for applications in nanomedicine.

[This corrects the article DOI: 10.1039/C8SC02847H.].

Branched Aluminum Nanocrystals with Internal Hot Spots: Synthesis and Single-Particle Surface-Enhanced Raman Scattering.

Owing to their unique and sustainable surface plasmonic properties, Al nanocrystals have attracted increasing attention for plasmonic-enhanced applications, including single-particle surface-enhanced Raman scattering (SERS). However, whether Al nanocrystals can achieve single-particle SERS is still unknown, mainly due to the synthetic difficulty of Al nanocrystals with internal gaps. Herein, we report a regrowth method for the synthesis of Al nanohexapods with tunable and uniform internal gaps for single-particle SERS with an enhancement factor of up to 1.79 × 108. The uniform branches of the Al nanohexapods can be systematically tuned regarding their dimensions, terminated facets, and internal gaps. The Al nanohexapods generate hot spots concentrated in the internal gaps due to the strong plasmonic coupling between the branches. A single-particle SERS measurement of Al nanohexapods shows strong Raman signals with maximum enhancement factors comparable to that of Au counterparts. The large enhancement factor indicates that Al nanohexapods are good candidates for single-particle SERS.

Heat shock protein family A member 8 serving as a co-activator of transcriptional factor ETV4 up-regulates PHLDA2 to promote the growth of liver cancer.

Heat shock protein family A member 8 (HSPA8) participates in the folding or degradation of misfolded proteins under stress and plays critical roles in cancer. In this study, we investigated the function of HSPA8 in the development of liver cancer. By analyzing the TCGA transcriptome dataset, we found that HSPA8 was upregulated in 134 clinical liver cancer tissue samples, and positively correlated with poor prognosis. IHC staining showed the nuclear and cytoplasmic localization of HSPA8 in liver cancer cells. Knockdown of HSPA8 resulted in a decrease in the proliferation of HepG2 and Huh-7 cells. ChIP-seq and RNA-seq analysis revealed that HSPA8 bound to the promoter of pleckstrin homology-like domain family A member 2 (PHLDA2) and regulated its expression. The transcription factor ETV4 in HepG2 cells activated PHLDA2 transcription. HSPA8 and ETV4 could interact with each other in the cells and colocalize in the nucleus. From a functional perspective, we demonstrated that HSPA8 upregulated PHDLA2 through the coactivating transcription factor ETV4 to enhance the growth of liver cancer in vitro and in vivo. From a therapeutic perspective, we identified both HSPA8 and PHDLA2 as novel targets in the treatment of HCC. In conclusion, this study demonstrates that HSPA8 serves as a coactivator of ETV4 and upregulates PHLDA2, leading to the growth of HCC, and is a potential therapeutic target in HCC treatment.

ALDH2 attenuates ischemia and reperfusion injury through regulation of mitochondrial fusion and fission by PI3K/AKT/mTOR pathway in diabetic cardiomyopathy.

The function of mitochondrial fusion and fission is one of the important factors causing ischemia-reperfusion (I/R) injury in diabetic myocardium. Aldehyde dehydrogenase 2 (ALDH2) is abundantly expressed in heart, which involved in the regulation of cellular energy metabolism and stress response. However, the mechanism of ALDH2 regulating mitochondrial fusion and fission in diabetic myocardial I/R injury has not been elucidated. In the present study, we found that the expression of ALDH2 was downregulated in rat diabetic myocardial I/R model. Functionally, the activation of ALDH2 resulted in the improvement of cardiac hemodynamic parameters and myocardial injury, which were abolished by the treatment of Daidzin, a specific inhibitor of ALDH2. In H9C2 cardiomyocyte hypoxia-reoxygenation model, ALDH2 regulated the dynamic balance of mitochondrial fusion and fission and maintained mitochondrial morphology stability. Meanwhile, ALDH2 reduced mitochondrial ROS levels, and apoptotic protein expression in cardiomyocytes, which was associated with the upregulation of phosphorylation (p-PI3KTyr458, p-AKTSer473, p-mTOR). Moreover, ALDH2 suppressed the mitoPTP opening through reducing 4-HNE. Therefore, our results demonstrated that ALDH2 alleviated the ischemia and reperfusion injury in diabetic cardiomyopathy through inhibition of mitoPTP opening and activation of PI3K/AKT/mTOR pathway.

Comparison of the long-term outcomes of patients with hepatocellular carcinoma within the Milan criteria treated by ablation, resection, or transplantation.

BACKGROUND: Liver transplantation (LT), resection (LR), and ablation (LA) are three curative-intent treatment options for patients with early hepatocellular carcinoma (HCC). We aimed to develop a prognostic calculator to compare the long-term outcomes following each of these therapies. METHODS: A total of 976 patients with HCC within the Milan criteria who underwent LT, LR, and LA between 2009 and 2019 from four institutions were evaluated. Multistate competing risks prediction models for recurrence-free survival (RFS), recurrence within the Milan criteria (RWM), and HCC-specific survival (HSS) were derived to develop a prognostic calculator. RESULTS: During a median follow-up of 51 months, 420 (43%) patients developed recurrence. In the multivariate analysis, larger tumor size, multinodularity, older age, male, higher alpha-fetoprotein (AFP), higher albumin-bilirubin (ALBI) grade, and the presence of portal hypertension were significantly associated with higher recurrence and decreased survival rates. The RFS and HSS were both significantly higher among patients treated by LT than by LR or LA and significantly higher between patients treated by LR than by LA (all p < 0.001). For multinodular HCC ≤3 cm, although LT had better RFS and HSS than LR or LA, LA was noninferior to LR. An online prognostic calculator was then developed based on the preoperative clinical factors that were independently associated with outcomes to evaluate RFS, RWM, and HSS at different time intervals for all three treatment options. CONCLUSIONS: Although LT resulted in the best recurrence and survival outcomes, LR and LA also offered durable long-term alternatives. This prognostic calculator is a useful tool for clinicians to guide an informed and personalized discussion with patients based on their tumor biology and liver function.

Vibratome sectioning of tumors to evaluate the interactions between nanoparticles and the tumor microenvironment ex-vivo.

Nanoparticles have been investigated as drug carriers and promising agents for cancer therapy. However, the tumor microenvironment (TME), which is formed by the tumor, is considered a barrier for nanocarriers to enter the internal tumor tissue. Therefore, the evaluation of the biological distribution of nanocarriers in TME can provide useful information on their role in tumor-targeted drug delivery. Although the tumor-bearing mouse model is commonly used to investigate the distribution of nanocarriers in the TME, there is currently a lack of a testing system to predict the distribution of nanocarriers in tumor tissues, especially in patients. This study revealed that the macrophages and dendritic cells (DCs) were more distributed in the peripheral part than the central part of the tumor, which might be an obstacle to the uniform distribution of nanoparticles in the tumor. In addition, the cellular uptake of gold nanoparticles (AuNR and AuNS) in macrophages and DCs cell lines (RAW264.7 and DC1.2) was markedly different from that in the TME. Hence, the study model of the interaction between nanoparticles and macrophages and DCs has an important impact on the accuracy of the results. The vibratome sections of tumor tissues preserved the spatial distribution of immune cells and tumor cells, and had very little effects on their morphologies and activities. More importantly, we found that the distribution of nanocarriers in vibratome sections was similar to that in tumors in vivo. In all, ex vivo analysis using vibratome sections of tumor tissues provides a more convenient and stable method for elucidating the influences of TME on the distribution of nanocarriers.

A Novel Nomogram Model to Predict the Recurrence-Free Survival and Overall Survival of Hepatocellular Carcinoma.

Background: Treatments for patients with early-stage hepatocellular carcinoma (HCC) include liver transplantation (LT), liver resection (LR), radiofrequency ablation (RFA), and microwave ablation (MWA), are critical for their long-term survival. However, a computational model predicting treatment-independent prognosis of patients with HCC, such as overall survival (OS) and recurrence-free survival (RFS), is yet to be developed, to our best knowledge. The goal of this study is to identify prognostic factors associated with OS and RFS in patients with HCC and develop nomograms to predict them, respectively. Methods: We retrospectively retrieved 730 patients with HCC from three hospitals in China and followed them up for 3 and 5 years after invasive treatment. All enrolled patients were randomly divided into the training cohort and the validation cohort with a 7:3 ratio, respectively. Independent prognostic factors associated with OS and RFS were determined by the multivariate Cox regression analysis. Two nomogram prognostic models were built and evaluated by concordance index (C-index), calibration curves, area under the receiver operating characteristics (ROC) curve, time-dependent area under the ROC curve (AUC), the Kaplan-Meier survival curve, and decision curve analyses (DCAs), respectively. Results: Prognostic factors for OS and RFS were identified, and nomograms were successfully built. Calibration discrimination was good for both the OS and RFS nomogram prediction models (C-index: 0.750 and 0.746, respectively). For both nomograms, the AUC demonstrated outstanding predictive performance; the DCA shows that the model has good decision ability; and the calibration curve demonstrated strong predictive power. The nomograms successfully discriminated high-risk and low-risk patients with HCC associated with OS and RFS. Conclusions: We developed nomogram survival prediction models to predict the prognosis of HCC after invasive treatment with acceptable accuracies in both training and independent testing cohorts. The models may have clinical values in guiding the selection of clinical treatment strategies.

Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease featured to mitochondrial dysfunction in neuronal cells. Dynamin-related protein 1 (Drp1) is an important regulator of mitochondrial fission and subsequent mitophagy. Mangiferin (MGF) is a glucosyl xanthone mainly derived from Mangifera indica L., possessing multifaceted properties, e.g., antioxidant, anti-inflammatory, and enhancement of cognitive ability. Besides, it can cross the blood-brain barrier, thereby exerting a neuroprotective effect. However, so far, MGF's effect in balancing mitochondrial homeostasis via regulation of Drp1 level and mitophagic pathway in PD remains rarely reported. PURPOSE: We aimed to investigate the neuroprotective effect of MGF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and examine the possible mechanisms. METHODS: We utilized C57BL/6 mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Behavioral parameters, containing the open field test, balance beam, pole test, and rotarod test, assessed the locomotor activity; immunohistochemistry assessed the number of TH-positive neurons; transmission electron microscopy detected ultrastructural mitochondrial morphology in the dopaminergic neuron; complex I enzymatic activity microplate assay kit measured the mitochondrial complex I activity; ATP determination kit measured ATP levels in mitochondria isolated from cells or striatal tissues; western blot measured the levels of Drp1 and mitophagic proteins. RESULTS: We observed that MGF could mitigate motor deficiency and improve the expression of tyrosine hydroxylase in the substantia nigra of MPTP-induced PD mice. Furthermore, MGF not only ameliorated mitochondrial ultrastructure, but also improved mitochondrial ATP content. Within mitochondria, MGF could reduce Drp1 expression and reverse the expressions of mitophagic proteins, including PINK1, Parkin, NIX, BNIP3, FUNDC1, and p62. CONCLUSION: Present study indicates that MGF benefits mitochondrial networks by recovering mitochondrial ultrastructure and ATP contents, reducing mitochondrial Drp1, and modulating mitophagic proteins in the MPTP-induced PD mice model, which revealed a novel acting mechanism of MGF in PD's treatment.

Physisorption of Poly(ethylene glycol) on Inorganic Nanoparticles.

Poly(ethylene glycol) (PEG) is the most widely used polymer to decorate inorganic nanoparticles (NPs) by the "grafting-to" method for antifouling properties. PEG also shows diverse supramolecular interactions with nanoparticle surfaces and polar molecules, suggesting that the physisorption between PEG chains and NPs cannot be ignored in the "grafting-to" process. However, the effect of physisorption of PEG to NPs on the process of chemisorption has been rarely studied. Herein, we report that unfunctionalized PEG is physically adsorbed on various NPs by polyvalent supramolecular interactions, adopting "loop-and-train-tail" conformations. We investigated the effect of molecular weight of PEG and ligands of the NPs on the conformation of PEG chains by experimental methods and simulation. It is demonstrated that the physisorption of PEG on NPs can facilitate the chemisorption in the initial stages but delays it in the later stages during the "grafting-to" process. This work provides a deeper understanding of the conformation of physisorbed PEG on NPs and the relationship between physisorption and chemisorption.

Recurrent postmenopausal bleeding - just endometrial disease or ovarian sex cord-stromal tumor? A case report.

BACKGROUND: Postmenopausal bleeding (PMB) is a common gynecologic complaint among elderly women, and endometrial hyperplasia is a common cause of this bleeding. Ovarian fibromas are the most common type of ovarian sex cord-stromal tumor (SCST). They arise from non-functioning stroma, rarely show estrogenic activity, and stimulate endometrial hyperplasia, causing abnormal vaginal bleeding. CASE SUMMARY: We report herein the case of a 64-year-old Chinese woman who presented with recurrent PMB. A sex hormone test revealed that her estrogen level was significantly higher than normal, and other causes of hyperestrogenism had been excluded. The patient had undergone four curettage and hysteroscopy procedures in the past 7 years due to recurrent PMB and endometrial hyperplasia. The culprit behind the increase in estrogen level-an ovarian cellular fibroma with estrogenic activity-was eventually found during the fifth operation. CONCLUSION: Ovarian cellular fibromas occur insidiously, and some may have endocrine functions. Postmenopausal patients with recurrent PMB and endometrial thickening observed on ultrasonography are recommended to undergo sex hormone testing while waiting for results regarding the pathology of the endometrium. If the estrogen level remains elevated, the clinician should consider the possibility of an ovarian SCST and follow-up the patient closely, even if the imaging results do not indicate ovarian tumors. Once the tumor is found, it should be removed as soon as possible no matter the size to avoid endometrial lesions due to long-term estrogen stimulation. More studies are needed to confirm whether preventive total hysterectomy with bilateral salpingo-oophorectomy should be recommended for women with recurrent PMB exhibiting elevated estrogen levels, despite the auxiliary examination results not indicating ovarian mass. The physical and psychological burden caused by repeated curettage could be prevented using this technique.

Inflammatory and oxidative stress responses of healthy elders to solar-assisted large-scale cleaning system (SALSCS) and changes in ambient air pollution: A quasi-interventional study in Xi'an, China.

An outdoor solar assisted large-scale cleaning system (SALSCS) was constructed to mitigate the levels of fine particulate matter (PM2.5) in urban areas of Xi'an China, providing a quasi-experimental opportunity to examine the biologic responses to the changes in pollution level. We conducted this outdoor SALSCS based real-world quasi-interventional study to examine the associations of the SALSCS intervention and changes in air pollution levels with the biomarkers of systemic inflammation and oxidative stress in healthy elders. We measured the levels of 8-hydrox-2-deoxyguanosine (8-OHdG), Interlukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α) from urine samples, and IL-6 from saliva samples of 123 healthy retired participants from interventional/control residential areas in two sampling campaigns. We collected daily 24-h PM2.5 samples in two residential areas during the study periods using mini-volume samplers. Data on PM10, gaseous pollutants and weather factors were collected from the nearest national air quality monitoring stations. We used linear mixed-effect models to examine the percent change in each biomarker associated with the SALSCS intervention and air pollution levels, after adjusting for time trend, seasonality, weather factors and personal characteristics. Results showed that the SALSCS intervention was significantly associated with decreases in the geometric mean of biomarkers by 47.6% (95% confidence interval: 16.5-67.2%) for 8-OHdG, 66% (31.0-83.3%) for TNF-α, 41.7% (0.2-65.9%) and 43.4% (13.6-62.9%) for urinary and salivary IL-6, respectively. An inter-quartile range increase of ambient PM2.5 exposure averaged on the day of the collection of bio-samples and the day before (34.1 µg/m3) was associated, albeit non-significantly so, with 22.8%-37.9% increases in the geometric mean of these biomarkers. This study demonstrated that the SALSCS intervention and decreased ambient air pollution exposure results in lower burden of systemic inflammation and oxidative stress in older adults.

Accurate identification and surgical correction of type IIb uterine malformation using synchronized hysteroscopy and laparoscopy.

OBJECTIVE: To introduce an effective approach for accurate identification and treatment of type IIb uterine malformation using synchronized hysteroscopy and laparoscopy. DESIGN: Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique. The patient provided written informed consent for video and data collection for research purposes. The study was approved by the local ethics committee of Shengjing Hospital of China Medical University. SETTING: Academic medical center. PATIENT(S): A 32-year-old young woman diagnosed with a right unicornuate uterus with a left rudimentary horn, with a 2-year history of dysmenorrhea. INTERVENTION(S): First, the patient was diagnosed with a unicornuate uterus with a rudimentary horn using ultrasonography and magnetic resonance imaging before the surgery. During surgery, synchronized hysteroscopy and laparoscopy coupled with a light test was performed to make a definite identification of the type IIb uterine malformation. During treatment of the type IIb uterine malformation, there were two key steps: resected the rudimentary horn and reserved more myometrial tissue to reduce the risk of uterine rupture in a subsequent pregnancy; and corrected the uterus to prevent future uterine prolapse. For the suture technique, suturing during resection was performed instead of suturing after complete resection to reduce the intraoperative bleeding as much as possible. Furthermore, tubal catheterization and hydrotubation under hysteroscopy monitoring were performed. MAIN OUTCOME MEASURE(S): Value and feasibility of synchronized hysteroscopic and laparoscopic identification and treatment of the type IIb uterine malformation. RESULT(S): The total operation time was 89 minutes. The postoperative pathological findings revealed that the endometrium was found in the rudimentary horn. No dysmenorrhea was found during follow-up. At 26 months after the operation, the patient became pregnant naturally. Cesarean section was performed at 36 weeks + 2 days owing to premature rupture of the membranes. CONCLUSION(S): For the accurate identification and management of a type IIb uterine malformation, synchronized hysteroscopy and laparoscopy is an effective and feasible method.

Novel laparoscopic surgery for the repair of cesarean scar defect without processing scar resection.

BACKGROUND: Cesarean scar defect (CSD), especially CSD with residual myometrium less than 3 mm is reported to be the highest risk agent associated with uterine rupture for subsequent pregnancy. Currently, laparoscopic resection and suture was the mainstay therapy method for CSD with a residual myometrium less than 3 mm in women with a desire to conceive. Besides, the women have CSD related symptoms, especially postmenstrual bleeding, should be recommended for CSD treatment. This study is to investigate the efficiency of this novel laparoscopic surgery for the repair of cesarean scar defect (CSD) without scar resection for residual myometrium thickening. METHOD: This retrospective clinical study enrolled 76 women diagnosed with CSD who had a residual myometrium thickness less than 3 mm and also had a desire to conceive, had undergone laparoscopic surgery for the repair of CSD in the time period March 2016 to March 2018. Two study cohorts were created among the 76 patients: 40 patients had undergone the novel laparoscopic repair of CSD without processing scar resection (Group A), whereas 36 patients had undergone the traditional laparoscopic resection and suture of CSD (Group B). RESULTS: Residual myometrium thickening occurred among all the 76 patients and the average residual myometrium thickness was increased to almost 6 mm, presenting no between-group difference. In Group A, all the CSD-related postmenstrual bleeding was resolved or improved, but one patient in Group B has no obvious change to postmenstrual bleeding. After CSD repair, 20 patients got pregnant naturally in Group A, and there was no cesarean scar pregnancy and uterine rupture. While, there were 9 cases of natural pregnancy in Group B. No uterine rupture occurred among these 9 pregnant women of Group B, but 1 case of pregnancy was terminated due to cesarean scar pregnancy. CONCLUSION: Laparoscopic repair without processing scar resection seems to be a feasible, safe and simple operative approach for CSD treatment, which can thicken residual myometrium and improve postmenstrual bleeding.

Serum albumin guided plasmonic nanoassemblies with opposite chiralities.

Chiral assemblies by combining natural biomolecules with plasmonic nanostructures hold great promise for plasmonic enhanced sensing, imaging, and catalytic applications. Herein, we demonstrate that human serum albumin (HSA) and porcine serum albumin (PSA) can guide the chiral assembly of gold nanorods (GNRs) with left-handed chiroptical responses opposite to those by a series of other homologous animal serum albumins (SAs) due to the difference of their surface charge distributions. Under physiological pH conditions, the assembly of HSA or PSA with GNRs yielded left-handed twisted aggregates, while bovine serum albumin (BSA), sheep serum albumin, and equine serum albumin behaved on the contrary. The driving force for the chiral assembly is mainly attributed to electrostatic interaction. The opposite chiroptical signals acquired are correlated with the chiral surface charge distributions of the tertiary structures of SAs. Moreover, the chirality of the assembly induced by both HSA and BSA can be enhanced or reversed by adjusting the pH values. This work provides new insights into the modulation of protein-induced chiral assemblies and promotes their applications.

θ-Solvent-Mediated Double-Shell Polyethylene Glycol Brushes on Nanoparticles for Improved Stealth Properties and Delivery Efficiency.

Antifouling polymer brushes are widely used to inhibit the formation of protein corona on nanoparticles (NPs) and subsequent accumulation in the liver and spleen. Herein, we demonstrate a θ-solvent-mediated method for the preparation of gold nanoparticles with a high polyethylene glycol (PEG) grafting density. Reaching the θ-solvent by adding salt (e.g., Na2SO4) can significantly increase the grafting density of the PEG brush to 2.08 chains/nm2. The PEG polymer brush prepared in the θ-solvent possesses a double-shell structure consisting of a concentrated polymer brush (CPB) and a semidilute polymer brush (SDPB), denoted as NP@CPB@SDPB, while those prepared in a good solvent have only a SDPB shell, i.e., NP@SDPB. Compared to the NP@SDPB structure, the NP@CPB@SDPB structure decreases the liver accumulation from 34.0%ID/g to 23.1%ID/g, leading to an increase in tumor accumulation from 8.5%ID/g to 12.8%ID/g. This work provides new insights from the perspective of polymer physical chemistry into the improved stealth properties and delivery efficiency of NPs, which will accelerate the clinical translation of nanomedicine.

Enhanced optical asymmetry in supramolecular chiroplasmonic assemblies with long-range order.

Chiral assemblies of plasmonic nanoparticles are known for strong circular dichroism but not for high optical asymmetry, which is limited by the unfavorable combination of electrical and magnetic field components compounded by strong scattering. Here, we show that these limitations can be overcome by the long-range organization of nanoparticles in a manner similar to the liquid crystals and found in helical assemblies of gold nanorods with human islet amyloid polypeptides. A strong, polarization-dependent spectral shift and the reduced scattering of energy states with antiparallel orientation of dipoles activated in assembled helices increased optical asymmetry g-factors by a factor of more than 4600. The liquid crystal-like color variations and the nanorod-accelerated fibrillation enable drug screening in complex biological media. Improvement of long-range order can also provide structural guidance for the design of materials with high optical asymmetry.

Endoscopic Treatment of Previous Cesarean Scar Defect in Women with Postmenstrual Bleeding: A Retrospective Cohort Study.

OBJECTIVE: To compare the incidence of postmenstrual bleeding after hysteroscopic resection versus laparoscopic repair of previous cesarean scar defect (PCSD). MATERIALS AND METHODS: Retrospective analysis of computerized patient records. For the diagnosis of PCSD, patients underwent transvaginal ultrasound first without and then with saline-assisted sonohysterography. Hysteroscopic PCSD resection was performed under sonographic guidance, while laparoscopic repair was guided by hysteroscopy for the confirmation of scar margins. RESULTS: Records of 62 patients presenting with PCSD-related postmenstrual bleeding were included in analysis. Hysteroscopic surgery had significantly shorter operative time compared to the laparoscopic approach (Mean =30.9 vs 71.0 minutes; p < 0.001). Blood loss and hospital stay were significantly less (p < 0.001) in hysteroscopic resection (10.4 ± 4.6 ml and 2.1 ± 0.4 days) than in laparoscopic repair (36.6 ± 4 ml, and 4.6 ± 1 days). After surgical interventions, the postmenstrual bleeding was resolved or improved. The effectiveness rates of hysteroscopic resection and laparoscopic repair were 91.4% and 96.3%, respectively. Incidence of post-treatment postmenstrual bleeding was not significantly different between hysteroscopy and laparoscopy (OR= 1.29 [95% confidence interval 0.367, 4.86]; p = 0.662). Pretreatment postmenstrual bleeding was associated with time since cesarean section (B= -0.091 [-0.158, -0.023]; p = 0.01) and PCSD length (B = 0.502 [0.085, 0.919]; p = 0.019). CONCLUSION: Both hysteroscopic resection and laparoscopic repair of PCSD yield comparable efficacy in reducing postmenstrual bleeding. However, hysteoroscopic resection of PCSD is associated with comparatively shorter operative time, less blood loss, and shorter hospital stay.