Evaluation of quality consistency between dispensing granules and traditional decoction of Bombyx batryticatus based on peptidomics and in silico simulations.

The application of traditional Chinese medicine dispensing granules is becoming increasingly prevalent. However, the consistency of dispensing granules with traditional decoction remains controversial. In this study, the consistency of peptide composition and pharmacodynamics between dispensing granules and traditional decoction of Bombyx batryticatus (BB) were assessed. A peptidomics method based on LC-tandem mass spectrometry technology was used to evaluate peptide composition similarity between BB traditional decoction and dispensing granules. The results revealed notable differences in peptide sequences between the two dosage forms, with only 8.55% of peptides shared between them. To evaluate the potential pharmacodynamic effects of the two dosage forms on epilepsy, virtual screening was used to identify potential active peptides, including blood-brain barrier permeability, toxicity prediction, and molecular docking. BB traditional decoction demonstrated a higher number and greater abundance of potential active peptides than BB dispensing granules, suggesting that BB traditional decoction may have a more favorable effect in treating epilepsy compared with BB dispensing granules. Moreover, molecular docking and molecular dynamics simulation studies confirmed the mechanism of action of active peptides to γ-aminobutyric acid transporter 1 (GAT-1). This study provides a scientific basis for the evaluation of quality consistency between BB traditional decoction and dispensing granules.

Adjuvant chemotherapy improves long-term survival in pathologic stage III rectal mucinous adenocarcinoma after pre-operative chemoradiotherapy.

PURPOSE: The benefits of adjuvant chemotherapy remain debated rectal mucinous adenocarcinoma (MC). Our study aims to delve into the efficacy of adjuvant chemotherapy in pathologic stage III rectal MC by a large population-based database. METHODS: The Chi-square test was performed to examine the parameters between treatment groups. The overall survival (OS) and cancer-specific survival (CSS) of treatment groups were conducted by using the Kaplan-Meier method. The impact of factors on survival was assessed using Cox regression analyses. To balance the covariates and reduce the selection bias, we employed propensity score matching (PSM) to narrow the differences between treatment groups. RESULTS: The median follow-up time for overall patients was 80 months. In the pre-operative chemoradiotherapy (pre-CRT) group, patients who received adjuvant chemotherapy had significantly better 5-year OS and CSS. Multivariate analyses found that adjuvant chemotherapy was associated with better OS (p < 0.001, HR (95% CI): 0.66 (0.51-0.86)) and CSS (p = 0.012, HR (95% CI): 0.71 (0.54-0.93)). However, adjuvant chemotherapy was not an independent prognosis factor in both OS (p = 0.149, HR (95% CI): 0.76 (0.53-1.1); Supplement Table 1) and CSS (p = 0.183, HR (95% CI): 0.74 (0.48-1.15)) in patients who did not receive pre-CRT. After PSM, similar results were found in the pre-CRT and the no pre-CRT groups. CONCLUSION: In conclusion, our population-based retrospective cohort study indicates that the effects of adjuvant chemotherapy were associated with the pre-CRT status in patients with stage III rectal MC. In patients who underwent pre-CRT, the receipt of adjuvant chemotherapy was associated with better survival outcomes. Conversely, adjuvant chemotherapy does not seem to confer significant survival benefits to patients without pre-CRT.

The benefits of adjuvant chemotherapy are associated with the kind of neoadjuvant therapy in stage ypI rectal cancer: evidence based on population analysis.

PURPOSE: The oncological role of adjuvant chemotherapy (ACT) remains debated in locally advanced rectal cancer (RC) after neoadjuvant therapy (NAT), especially ypI RC. In this study, we used population-based data to evaluate the benefits of ACT in stage ypI RC after NAT and surgery. Moreover, we tried to differentiate what kind of NAT (radiotherapy alone or chemoradiotherapy) was administered because this may affect the further efficacy of ACT. METHODS: All patients with stage ypI primary rectal malignancy were diagnosed in the SEER database between 2004 and 2017. The Kaplan-Meier method was applied to estimate the effects of ACT in survival analysis. Cox regression was performed to calculate the hazard ratio (HR) and the prognosis factors of survival. Propensity score matching (PSM) was used to balance the parameters between therapy groups. RESULTS: The overall cohort's median follow-up time was 105 months. For 5-year OS and CSS, there were no significant differences between the ACT ( +) and ACT (-) groups (p = 0.105; p = 0.788). However, subgroup analyses according to the kind of NAT found that ACT improved overall survival (OS) and cancer-specific survival (CSS) in patients who received neoadjuvant radiotherapy (nRT) (p < 0.001, p = 0.015). Among patients who received neoadjuvant chemoradiotherapy (nCRT), no significant survival benefits were found between the ACT ( +) and ACT (-) groups (p = 0.526, p = 0.288). CONCLUSION: Our population-based cohort study suggested that the efficacy of ACT was associated with the kind of NAT. The ACT provides survival benefits in stage ypI RC for patients who received nRT. However, among patients who received nCRT, ACT did not improve long-term survival.

Derlin-1 exhibits oncogenic activities and indicates an unfavorable prognosis in breast cancer.

Derlin-1 is involved in the elimination of misfolded proteins and has been implicated in the progression of human cancers. However, its prognostic value and biological function in breast cancer remain unknown. Here, we show that Derlin-1 is overexpressed in breast cancer and exhibits oncogenic activities via interaction with UBE2C. Increased expression of Derlin-1 is correlated with lymph node metastasis, advanced clinical stage, and unfavorable overall survival in two cohorts containing over 1,000 patients. Multivariate analyses by the Cox regression model suggest Derlin-1 is an independent factor for poor prognosis. In vitro experiments demonstrate that Derlin-1 expression is transcriptionally upregulated by c-Myc. Ectopic expression of Derlin-1 promotes breast cancer cell proliferation and migration, whereas the knockdown of Derlin-1 results in the opposite phenotypes. Mechanistically, Derlin-1 directly binds to UBE2C to increase the phosphorylation of AKT and ERK. The treatment of UBE2C siRNA markedly attenuates Derlin-1-mediated cell growth and migration. Collectively, our data suggest Derlin-1 is a potential prognostic factor and functions as an oncogene in breast cancer.

Observation of Interference between Resonant and Detuned stirap in the Adiabatic Creation of

Stimulated Raman adiabatic passage (stirap) allows efficiently transferring the populations between two discrete quantum states and has been used to prepare molecules in their rovibrational ground state. In realistic molecules, a well-resolved intermediate state is usually selected to implement the resonant stirap. Because of the complex molecular level structures, the detuned stirap always coexists with the resonant stirap and may cause unexpected interference phenomenon. However, it is generally accepted that the detuned stirap can be neglected if compared with the resonant stirap. Here we report on the first observation of interference between the resonant and detuned stirap in the adiabatic creation of ^{23}Na^{40}K ground-state molecules. The interference is identified by observing that the number of Feshbach molecules after a round-trip stirap oscillates as a function of the hold time, with a visibility of about 90%. This occurs even if the intermediate excited states are well resolved, and the single-photon detuning of the detuned stirap is about 1 order of magnitude larger than the linewidth of the excited state and the Rabi frequencies of the stirap lasers. Moreover, the observed interference indicates that if more than one hyperfine level of the ground state is populated, the stirap prepares a coherent superposition state among them, but not an incoherent mixed state. Further, the purity of the hyperfine levels of the created ground state can be quantitatively determined by the visibility of the oscillation.

Biomechanical and Performance Evaluation of Magnetic Elliptical-Ring Compressive Anastomoses.

BACKGROUND: After magnetic compressive anastomosis, anastomat passage through the narrow channels of the digestive tract is difficult owing to the device's large volume. Such passage can lead to mechanical damage to the digestive tract or anastomat's unstable excretion time. This article presents a new magnetic compressive anastomotic approach. METHODS: A magnetic elliptical-ring compressive anastomat was designed and evaluated for placement and passage in vitro. Nine young adult dogs underwent laparotomy with intestinal tissue side-to-side anastomosis. Four different groups of magnetic compressive anastomats of two different magnetic force levels (20 N or 30 N) and shapes (round or elliptical) were implanted into each dog simultaneously. Three dogs were euthanized on each of postoperative day 1, day 4, and day 7. Anastomoses were then compared with respect to histology and tensile fracture force. RESULTS: The magnetic elliptical-ring compressive anastomat was functional but produced less obstruction compared to its round counterpart during passage through the esophagus and intestine. Nine dogs underwent successful surgery and harvesting of 30 total anastomoses. Histology of anastomotic tissue showed that, along the newly formed tunnel connecting the two sides of anastomotic tissues, compressed tissues became thinner and fell off, and initial anastomoses formed on the seventh postoperative day. There were large differences in tensile fracture force among the anastomoses formed by magnets with different magnetic forces of the same structure. However, the magnetic compressive anastomat structure did not affect anastomotic repair during magnetic compression anastomosis. CONCLUSIONS: The magnetic elliptical-ring compressive anastomat is an efficient anastomotic device that can be used easily and with good passage. The device has good biomechanical properties and can be used with endoscopy to reduce operative time.

Gelatin-based perfusable, endothelial carotid artery model for the study of atherosclerosis.

BACKGROUND: Carotid artery geometry is important for recapitulating a pathophysiological microenvironment to study wall shear stress (WSS)-induced endothelial dysfunction in atherosclerosis. Endothelial cells (ECs) cultured with hydrogel have been shown to exhibit in vivo-like behaviours. However, to date, studies using hydrogel culture have not fully recapitulated the 3D geometry and blood flow patterns of real-life healthy or diseased carotid arteries. In this study, we developed a gelatin-patterned, endothelialized carotid artery model to study the endothelium response to WSS. RESULTS: Two representative regions were selected based on the computational fluid dynamics on the TF-shaped carotid artery: Region ECA (external carotid artery) and Region CS (carotid sinus). Progressive elongation and alignment of the ECs in the flow direction were observed in Region ECA after 8, 16 and 24 h. However, the F-actin cytoskeleton remained disorganized in Region CS after 24 h. Further investigation revealed that expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was greatly increased in Region CS relative to that in Region ECA. The physiological WSS in the carotid artery system was found to stimulate nitric oxide (NO) and prostacyclin (PGI2) release and inhibit endothelin-1 (ET-1) release after 24-h perfusion experiments. The effective permeability (E.P) of fluorescein isothiocyanate (FITC)-dextran 40 kDa in Regions ECA and CS was monitored, and it was found that the turbulence WSS value (in Region CS) was less than 0.4 Pa, and there was a significant increase in the E.P relative to that in Region ECA, in which laminar WSS value was 1.56 Pa. The tight junction protein (ZO-1) production was shown that the low WSS in Region CS induced ZO-1-level downregulation compared with that in Region ECA. CONCLUSIONS: The results suggested that the gelatin-based perfusable, endothelial carotid artery model can be effective for studying the pathogenesis of atherosclerosis by which flow dynamics control the endothelium layer function in vitro.

A study of cryogenic tissue-engineered liver slices in calcium alginate gel for drug testing.

To address issues such as transportation and the time-consuming nature of tissue-engineered liver for use as an effective drug metabolism and toxicity testing model, "ready-to-use" cryogenic tissue-engineered liver needs to be studied. The research developed a cryogenic tissue-engineered liver slice (TELS), which comprised of HepG2 cells and calcium alginate gel. Cell viability and liver-specific functions were examined after different cryopreservation and recovery culture times. Then, cryogenic TELSs were used as a drug-testing model and treated with Gefitinib. Cryogenic TELSs were stored at -80 °C to ensure high cell viability. During recovery in culture, the cells in the cryogenic TELS were evenly distributed, massively proliferated, and then formed spheroid-like aggregates from day 1 to day 13. The liver-specific functions in the cryogenic TELS were closely related to cryopreservation time and cell proliferation. As a reproducible drug-testing model, the cryogenic TELS showed an obvious drug reaction after treatment with the Gefitinib. The present study shows that the cryopreservation techniques can be used in drug-testing models.

A Noise Removal Method for Uniform Circular Arrays in Complex Underwater Noise Environments with Low SNR.

Generally, many beamforming methods are derived under the assumption of white noise. In practice, the actual underwater ambient noise is complex. As a result, the noise removal capacity of the beamforming method may be deteriorated considerably. Furthermore, in underwater environment with extremely low signal-to-noise ratio (SNR), the performances of the beamforming method may be deteriorated. To tackle these problems, a noise removal method for uniform circular array (UCA) is proposed to remove the received noise and improve the SNR in complex noise environments with low SNR. First, the symmetrical noise sources are defined and the spatial correlation of the symmetrical noise sources is calculated. Then, based on the preceding results, the noise covariance matrix is decomposed into symmetrical and asymmetrical components. Analysis indicates that the symmetrical component only affect the real part of the noise covariance matrix. Consequently, the delay-and-sum (DAS) beamforming is performed by using the imaginary part of the covariance matrix to remove the symmetrical component. However, the noise removal method causes two problems. First, the proposed method produces a false target. Second, the proposed method would seriously suppress the signal when it is located in some directions. To solve the first problem, two methods to reconstruct the signal covariance matrix are presented: based on the estimation of signal variance and based on the constrained optimization algorithm. To solve the second problem, we can design the array configuration and select the suitable working frequency. Theoretical analysis and experimental results are included to demonstrate that the proposed methods are particularly effective in complex noise environments with low SNR. The proposed method can be extended to any array.

Telomere reverse transcriptase (TERT) rs2735940 increases cancer risk.

BACKGROUND: Telomerase reverse transcriptase (TERT) rs2735940 polymorphism was found to be associated with increased cancer risk. However, recent studies reported controversial results. The aim of our study was to detect its relationship with cancer risk. MATERIAL AND METHODS: EMBASE and PubMed databases were searched for all publications until October 2014. ORs and 95% CIs were applied to investigate the association in the random-effects model. RESULTS: Thirteen case-control studies with 19385 cases and 17558 controls were included in this study. We found a significant association between cancer risk and TERT rs2735940 polymorphism (OR=1.06, 95% CI 1.02-1.11, P=0.005). In the subgroup analysis by ethnicity, a marginal association was found in Caucasians (OR=1.05, 95% CI 1.00-1.10, P=0.05), but not in Asians (OR=1.01, 95% CI 0.82-1.24, P=0.93). In the subgroup analysis by cancer site, this polymorphism was significantly associated with lung cancer risk (OR=1.08, 95% CI 1.02-1.13, P=0.004). CONCLUSIONS: TERT rs2735940 polymorphism was significantly associated with cancer risk, especially lung cancer.

Sequential assembly of 3D perfusable microfluidic hydrogels.

Bottom-up tissue engineering provides a promising way to recreate complex structural organizations of native organs in artificial constructs by assembling functional repeating modules. However, it is challenging for current bottom-up strategies to simultaneously produce a controllable and immediately perfusable microfluidic network in modularly assembled 3D constructs. Here we presented a bottom-up strategy to produce perfusable microchannels in 3D hydrogels by sequentially assembling microfluidic modules. The effects of agarose-collagen composition on microchannel replication and 3D assembly of hydrogel modules were investigated. The unique property of predefined microchannels in transporting fluids within 3D assemblies was evaluated. Endothelial cells were incorporated into the microfluidic network of 3D hydrogels for dynamic culture in a house-made bioreactor system. The results indicated that the sequential assembly method could produce interconnected 3D predefined microfluidic networks in optimized agarose-collagen hydrogels, which were fully perfusable and successfully functioned as fluid pathways to facilitate the spreading of endothelial cells. We envision that the presented method could be potentially used to engineer 3D vascularized parenchymal constructs by encapsulating primary cells in bulk hydrogels and incorporating endothelial cells in predefined microchannels.

[The development of the system of blood flow block by using magnetic compression abdominal large vascular].

A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.

Unraveling the intercorrelation between pseudo-graphitic phase and Li+/Na+ migration behavior in semicoke-based carbon anodes.

Microstructural engineering is regarded as a promising option for fabricating high-performance carbon anodes. Hence, a facile solvothermal-assisted low-temperature calcination strategy was employed to modulate the microstructure of semicoke-derived carbon anodes. Owing to the effective pseudo-graphite phase modulation, the modified carbon anode exhibited a significant increase in capacity, cycling stability and ion kinetics in both lithium-ion batteries and sodium-ion batteries. Kinetic analysis and in-situ X-ray diffraction confirmed the "adsorption and intercalation" energy storage mechanism of the obtained carbon electrodes. In addition, by investigating the energy storage mechanism, we found that increasing the pseudo-graphite phase proportion played different roles in lithium and sodium ions storage. For lithium-ion storage, the pseudo-graphitic phase preferentially promotes lithium-ion transport kinetics. Conversely, during sodium-ion storage, this particular structure markedly augments the embedding capacity of sodium. Theoretical calculations demonstrate that different patterns of variation in the activation energy with the carbon layer spacing of lithium/sodium intercalation compounds lead to differences in performance enhancement. This study not only offers a low-cost approach for preparing carbon anodes enriched with a pseudo-graphitic phase, but also provides new insight into the discrepancy between lithium ion and sodium ion storage.

3D-printed silicate porous bioceramics promoted the polarization of M2-macrophages that enhanced the angiogenesis in bone regeneration.

The failure of bone regeneration has been considered as a serious problem that troubling patients for decades, most of which was resulted by the poor angiogenesis and chronic inflammation after surgery. Among multiple materials applied in the repair of bone defect, silicate bioceramics attracted researchers because of its excellent bioactivity. The purpose of this study was to detect the effect of specific bioactive glass ceramic (AP40, based on crystalline phases of apatite and wollastonite) on angiogenesis and the subsequent bone growth through the modulation of macrophages. Two groups were included in this study: control group (macrophages without any stimulation, denominated as Control) and AP40 group (macrophages incubated on AP40). This study investigated the effect of AP40 on macrophages polarization (RAW264.7) and angiogenesis in vitro and in vivo. Additionally, the changes of angiogenic ability regulated by macrophages were explored. AP40 showed excellent angiogenesis potential and the expression of CD31 was promoted through the modulation of macrophages toward M2 subtype. Additionally, the macrophages incubated on AP40 synthesized more PDGF-BB comparing to macrophages without any stimulation, which contributed to the improved angiogenetic ability of human umbilical vein endothelial cells (HUVECs). Results of in vivo studies indicated increased bone ingrowth along the implants, which indicated the potential of bioceramics for bone defect repair clinically.

Calcium silicate/gelatin composite scaffolds with controllable degradation behavior: Fabrication and evaluation.

Calcium silicate can be used as an excellent material for biodegradable bone scaffolds because it can provide bioactive ions to promote bone regeneration. However, the brittleness and rapid degradation of calcium silicate scaffolds have significantly limited their clinical application. In this work, the calcium silicate scaffolds printed by DLP technology were immersed in a gelatin solution under high vacuum condition to obtain calcium silicate/gelatin composite scaffolds with good mechanical and biological properties. Then, genipin was used as a cross-linker for gelatin to control the degradation properties of the composite scaffolds. The initial compressive strength and toughness of the composite scaffolds were 5.0 times and one order of magnitude higher than those of the pure calcium silicate scaffolds, respectively. The gelatin on the surface of the scaffolds could effectively act as a protective layer to regulate the degradation behaviors of the calcium silicate substrate through controlling the crosslinking degree of the gelatin. After degrading for 14 days, the composite scaffolds at 1.0 % genipin concentration exhibited the highest compressive strength of 8.6 ± 0.8 MPa, much higher than that of the pure ceramic scaffold (1.5 ± 0.3 MPa). It can be found that the toughness of the composite scaffolds were almost over 13.2 times higher than that of the pure ceramic scaffold during degradation, despite the higher toughness loss for the former. Furthermore, the composite scaffolds showed enhanced cell biocompatibility and viability. These results demonstrate that the calcium silicate/gelatin composite scaffolds can be a promising candidate in bone tissue regeneration.

Radiotherapy is recommended for hormone receptor-negative older breast cancer patients after breast conserving surgery.

In this study, the necessity of radiotherapy (RT) for hormone receptor-negative older breast cancer patients after breast-conserving surgery (BCS) was investigated. The data of hormone receptor-negative invasive breast cancer patients who underwent BCS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were separated into two groups, namely, the RT group and the no radiotherapy (No RT) group. The 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were compared between the No RT and RT groups after propensity score matching (PSM). The nomograms for predicting the survival of patients were constructed from variables identified by univariate or multivariate Cox regression analysis. A total of 2504 patients were enrolled in the training cohort, and 630 patients were included in the validation cohort. After PSM, 738 patients were enrolled in the No RT group and RT group. We noted that RT can improve survival in hormone receptor-negative older breast cancer patients who undergo BCS. Based on the results of multivariate Cox analysis, age, race, tumour grade, receipt of RT and chemotherapy, pathological T stage, N status, M status and HER2 status were linked to OS and CSS for these patients, and nomograms for predicting OS and CSS were constructed and validated. Moreover, RT improved OS and CSS in hormone receptor-negative older breast cancer patients who underwent BCS. In addition, the proposed nomograms more accurately predicted OS and CSS for hormone receptor-negative older breast cancer patients after BCS.

Reproducibility in nontarget screening (NTS) of environmental emerging contaminants: Assessing different HLB SPE cartridges and instruments.

Non-targeted screening (NTS) methods are integral in environmental research for detecting emerging contaminants. However, their efficacy can be influenced by variations in hydrophilic-lipophilic balance (HLB) solid phase extraction (SPE) cartridges and high-resolution mass spectrometry (HRMS) instruments across different laboratories. In this study, we scrutinized the influence of five HLB SPE cartridges (Nano, Weiqi, CNW, Waters, and J&K) and four LC-HRMS platforms (Agilent, Waters, Thermo, and AB SCIEX) on the identification of emerging environmental contaminants. Our results demonstrate that 87.6 % of the target compounds and over 59.6 % of the non-target features were consistently detected across all tested HLB cartridges, with an overall 71.2 % universally identified across the four LC-HRMS systems. Discrepancies in detection rates were primarily attributable to variations in retention time stability, mass stability of precursors and fragments, system cleanliness affecting fold change and p-values, and fragment response. These findings confirm the necessity of refining parameter criteria for NTS. Moreover, our study confirms the efficacy of the PyHRMS tool in analyzing and processing data from multiple instrumental platforms, reinforcing its utility for multi-platform NTS. Overall, our findings underscore the reliability and robustness of NTS methods in identifying potential water contaminants, while also highlighting factors that may influence these outcomes.

Effect of Sulfur Modification on Structural and Electrochemical Performance of Pitch-Based Carbon Materials for Lithium/Sodium Ion Batteries.

Coal tar pitch (CTP) has become an ideal choice in the preparation of anode precursors for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of its abundant carbon content, competitive pricing and adjustable structure properties. In this paper, sulfurized pitch-based carbon (SPC-800) was obtained by allowing CTP to react with sulfur at 350 °C and subsequently achieve carbonization at 800 °C. SPC-800 was more disordered and had a larger layer spacing than carbonized CTP (PC-800). Upon utilization as an anode for LIBs, SPC-800 possessed a higher reversible specific capacity (478.1 mAh g-1 at 0.1 A g-1), while utilization in SIBs displayed a capacity of 220.9 mAh g-1 at 20 mA g-1. This work is an important guide to the design of high-performance anodes suitable for use with both LIBs and SIBs.

Risk stratification of stage II rectal mucinous adenocarcinoma to predict the benefit of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery.

Background: The treatment strategy for stage II rectal mucinous adenocarcinoma (RMA) recommends neoadjuvant chemoradiotherapy (NCR) followed by total mesorectal excision (TME). However, the necessity of adjuvant chemotherapy (AC) remains controversial. Materials and methods: Chi-square test was used to assess the relationship between pathological classification, AC and clinicopathological characteristics. Kaplan-Meier (KM) curves and the log-rank test were utilized to analyze differences in overall survival (OS) and cancer-specific survival (CSS) among different groups. Cox regression identified prognostic factors. Nomogram was established utilizing the independent prognostic factors. X-tile divided patients into three risk subgroups. Results: Compared to RMA, rectal adenocarcinoma (RA) demonstrates longer OS and CSS in all and non-AC stage II patients, with no difference in OS and CSS for AC stage II patients. Propensity score matching analyses yielded similar results. Stratified analysis found that AC both improve OS of RA and RMA patients. Age, gender, pathologic T stage, regional nodes examined, and tumor size were identified as independent prognostic factors for RMA patients without AC. A nomogram was constructed to generate risk scores and categorize RMA patients into three subgroups based on these scores. KM curves revealed AC benefits for moderate and high-risk groups but not for the low-risk group. The external validation cohort yielded similar results. Conclusions: In summary, our study suggests that, compared to stage II RA patients, stage II RMA patients benefit more from AC after NCR. AC is recommended for moderate and high-risk stage II RMA patients after NCR, whereas low-risk patients do not require AC.

A differential-targeting core-shell microneedle patch with coordinated and prolonged release of mangiferin and MSC-derived exosomes for scarless skin regeneration.

Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes. This material choice provides several benefits: the GelMA shell provides a swelling interface for tissue interlocking and rapid release of mangiferin at an early wound healing stage for anti-inflammation, whereas the PGLADMA core offers long-term encapsulation and release of exosomes (30% release in 3 weeks), promoting sustained angiogenesis and anti-inflammation. Our results demonstrate that the core-shell microneedle possesses anti-inflammatory properties and can induce angiogenesis both in vitro in terms of macrophage polarization and tube formation of human umbilical vein endothelial cells (HUVECs), and in vivo in terms of anti-inflammation, re-epithelization, and vessel formation. Importantly, we also observe reduced scar formation in vivo. Altogether, the degradation dynamics of our hydrophilic/hydrophobic materials enable the design of a core-shell microneedle for differential and prolonged release, promoting scarless skin regeneration, with potential for other therapies of long-term exosome release.