Room-Temperature CuI-Catalyzed N-Arylation of Cyclopropylamine.

A general and efficient CuI/N-carbazolyl-1H-pyrrole-2-carbohydrazide catalyst system was developed for the N-arylation of cyclopropylamine using aryl bromides at room temperature. Herein, 5 mol % CuI and 5 mol % of the ligand were used to synthesize N-aryl cyclopropylamines in moderate to excellent yields. This protocol was scaled up to produce the desired product at gram levels and has been generalized for C-N coupling between aryl bromides and amines at room temperature.

Inhibitory effect of liriopesides B in combination with gemcitabine on human pancreatic cancer cells.

Gemcitabine (GEM) is a standard chemotherapeutic agent for patients with pancreatic cancer; however, GEM-based chemotherapy has a high rate of toxicity. A combination of GEM and active constituents from natural products may enhance its therapeutic efficacy and reduce its toxicity. This study investigated the synergistic effects of the combination of liriopesides B (LirB) from Liriope spicata var. prolifera and GEM on human pancreatic cancer cells. The results of our study showed that the combination of LirB and GEM synergistically decreased the viability of pancreatic cancer cells. The combination also caused a strong increase in apoptosis and a strong decrease in cell migration and invasion. Furthermore, LirB combined with GEM had potent inhibitory effects on pancreatic cancer stem cells (CSCs). Studies on the mechanisms of action showed that the combination more potently inhibited protein kinase B (Akt) and nuclear factor kappa B (NF-κB), as well as the downstream antiapoptotic molecules B-cell lymphoma 2 (Bcl-2) and survivin than either agent used alone. The results of this study suggest that the combination of LirB with GEM may improve the efficacy of GEM for the treatment of pancreatic cancer.

A Novel Method for the Rat Model of Abdominal Aortic Aneurysm Induced by Retroperitoneal Implantation of an Osmotic Pump System With Lipopolysaccharide.

BACKGROUND: Few methods can cocurrently mimic the pathological characteristics and nature history of human abdominal aortic aneurysms (AAAs), especially for the exist of the self-healing tendency of rodents. This study tested a novel method for the AAA rat model induced by retroperitoneal implantation of an osmotic pump system with lipopolysaccharide (LPS) based on the hypothesis that chronic inflammation of perivascular adipose tissue directly influenced the development and progression of AAAs. METHODS: 20 male Sprague-Dawley rats (10-month-old) fed with the Paigen diet were randomly divided into 4 groups: the blank group ×2, the sham group ×4, the empty capsule group ×4, and the LPS capsule group ×10. The LPS capsule group received implantations of the ALZET® osmotic pump capsule with LPS (3.6 µg/day) parallel to the abdominal aorta through a retroperitoneal approach. Two weeks later, 6 rats were randomly selected from the LPS capsule group to form the anti-inflammatory group and received implantations of another osmotic pump capsule with interleukin (IL)-10 (75 ng/day) through the same approach. The changes in abdominal aortic diameter were observed by ultrasound every 2 weeks, and samples were harvested for histopathologic and immunohistochemical analysis 6 weeks later. RESULTS: Within the 6 weeks after modeling, the LPS capsule group showed sustained and significant aortic dilatation (P < 0.01), while the anti-inflammatory group showed a rapid and obvious shrinkage 2 weeks after the IL-10 osmotic pump capsule implantation (P < 0.01). The LPS capsule group presented excellent pathological mimicking of human AAAs and showed severe medial degeneration with the least elastic content among the 5 groups at the end of the sixth week (P < 0.05). Notably, the anti-inflammatory group showed perfect medial preservation with the most elastic content (P < 0.05) and the highest elastin/collagen ratio (P < 0.01) at the end of the study. Matrix metalloproteinases (MMP) 2 and 9 and toll-like receptor 2 showed strong expression in the LPS capsule group at the end of the sixth week, which was significantly higher than that in the blank group and sham group. Interestingly, the anti-inflammatory group showed a slightly higher MMP9 expression than the LPS capsule group though there was no statistical difference between them. CONCLUSIONS: This novel method for the rat AAA model induced by retroperitoneal implantation of an osmotic pump capsule with LPS can concurrently mimic the histological characteristics and natural history of human AAAs. Further studies were needed to improve the osmotic pump system.

Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study.

OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.

Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

BACKGROUND: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. METHODS: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. RESULTS: The surgical and instrument operation times were significantly shorter in the 3D printing group (p < 0.001). The 3D printing group exhibited significantly lower intraoperative fluoroscopy frequency and blood loss (p = 0.001 and p < 0.001, respectively). No significant differences were observed between the two groups in terms of fracture reduction quality, fracture healing time, preoperative pain scores (NRS scores), and 6-month hip joint function (Harris scores) (p > 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p < 0.05). Although the incidence of complications was lower in the 3D printing group (18.8% vs. 33.3%), the difference did not reach statistical significance (p = 0.433). CONCLUSION: Combining 3D printing with individualized custom-made metal plates for acetabular posterior wall and column fractures reduces surgery and instrument time, minimizes intraoperative procedures and blood loss, enhancing long-term hip joint function recovery. CLINICAL TRIAL REGISTRATION: 12/04/2023;Trial Registration No. ChiCTR2300070438; http://www.chictr.org.cn .

Coronary artery segmentation in CCTA images based on multi-scale feature learning.

BACKGROUND: Coronary artery segmentation is a prerequisite in computer-aided diagnosis of Coronary Artery Disease (CAD). However, segmentation of coronary arteries in Coronary Computed Tomography Angiography (CCTA) images faces several challenges. The current segmentation approaches are unable to effectively address these challenges and existing problems such as the need for manual interaction or low segmentation accuracy. OBJECTIVE: A Multi-scale Feature Learning and Rectification (MFLR) network is proposed to tackle the challenges and achieve automatic and accurate segmentation of coronary arteries. METHODS: The MFLR network introduces a multi-scale feature extraction module in the encoder to effectively capture contextual information under different receptive fields. In the decoder, a feature correction and fusion module is proposed, which employs high-level features containing multi-scale information to correct and guide low-level features, achieving fusion between the two-level features to further improve segmentation performance. RESULTS: The MFLR network achieved the best performance on the dice similarity coefficient, Jaccard index, Recall, F1-score, and 95% Hausdorff distance, for both in-house and public datasets. CONCLUSION: Experimental results demonstrate the superiority and good generalization ability of the MFLR approach. This study contributes to the accurate diagnosis and treatment of CAD, and it also informs other segmentation applications in medicine.

The tumour-associated stroma correlates with poor clinical outcomes and immunoevasive contexture in patients with upper tract urothelial carcinoma: results from a multicenter real-world study (TSU-01 Study).

BACKGROUND: In this real-world study, we aimed to elucidate the predictive value of tumour-associated stroma for clinical prognostic and therapeutic response in upper tract urothelial carcinoma (UTUC) by reviewing the clinicopathologic characteristics of 1015 UTUC patients through a nationwide multicenter analysis. METHODS: The tumour-stroma ratio (TSR) was assessed based on tissue sections stained for hematoxylin and eosin (H&E), and patients were further stratified into stroma-high (>50% stroma) and stroma-low group (≤50% stroma). Kaplan-Meier curve and Cox regression hazard analysis were conducted to assess the survival outcomes of UTUC patients. Bioinformatics analysis and immunostaining analysis were applied to portray the tumour microenvironment (TME). RESULTS: Stroma-high UTUC was significantly associated with poorer survival outcomes and inferior chemotherapeutic responsiveness. Our established nomogram achieved a high prognostic accuracy in predicting overall survival and cancer-specific survival in both of the discovery cohort (area under the curve [AUC] 0.663 and 0.712) and the validation cohort (AUC 0.741 and 0.747). Moreover, stroma-high UTUC was correlated with immunoevasive TME accompanied by increased cancer-associated fibroblasts, tumour-associated macrophages and, conspicuously a cluster of highly exhausted CD8+ T cells. CONCLUSION: Our results showed stroma-high UTUC was associated with an inferior prognosis and an immunoevasive TME with exhausted CD8+ T cells in UTUC patients. Our TSR-based nomogram could be used to refine prognosis and inform treatment decisions of patients with UTUC.

Consistent neutralization of circulating omicron sub-variants by hybrid immunity up to 6 months after booster vaccination.

The current COVID-19 vaccination program requires frequent booster vaccination to maintain sufficient neutralization levels against immune evasive SARS-CoV-2 variants. However, prior studies found more potent and durable immune response in convalescing individuals, raising the possibility of less frequent booster vaccination for them. Here, we conducted a longitudinal immunological study based on two prospective cohorts of booster vaccinated convalescing COVID-19 patients or healthcare workers (HCW) without COVID-19 history in Xiangyang, China. Comparing to 1-month post-boosting, pseudovirus neutralization titers (pVNT50) of ancestral Wuhan-Hu-1 and circulating omicron sub-variants BA.5, BF.7, BA.4.6, BA.2.75, and BA.2.75.2 spikes were stable or even increased in convalescing samples at 6-month post-boosting, when HCW samples showed substantial drop of neutralization titers across the spectrum. Variant-to-Wuhan-Hu-1 pVNT50 ratios showed no significant variation during the 17 months from pre-vaccination to 6-month post-boosting in convalescing individuals, indicating that the high durability of hybrid immunity was likely sustained by continuously improving neutralization potency that compensated immune decay. Our data provide mechanistic insight into prior epidemiological findings that vaccine-elicited humoral immune response was more durable in convalescing individuals than those without SARS-CoV-2 infection, and suggest further research into potential extension of boosting intervals for convalescing individuals.

Comparison of minimally invasive versus open pelvic organ-preserving radical cystectomy in female patients with bladder cancer: a multicenter propensity score matching analysis.

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.

Incidence and Prognostic Associations of Early Postoperative Stroke and Death Among Patients Undergoing Inner Branched Thoracic Endovascular Repair of Aortic Arch Pathologies: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this systematic review was to assess the incidences and associations of early postoperative stroke and death among patients undergoing inner branched thoracic endovascular aortic repair (TEVAR) of arch pathologies. METHODS: Electronic bibliographic sources (PUBMED, EMBASE, and CENTRAL) were searched up to February 2022 using a combination of thesaurus and free-text terms to identify the studies using branched TEVAR to treat aortic arch disease. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies investigating the prognosis of inner branched TEVAR in the treatment of aortic arch pathologies were included. Independent extraction of articles was performed by two authors using predefined data fields, including study quality indications. All pooled analyses were based on a random-effects or fixed model according to the heterogeneity. RESULTS: A total of 23 case series totaling 532 participants were included after screening. After optimized selection (largest sample size, most detailed data, lowest risk of bias) from the overlapping data, 12 studies with 289 participants were included in data synthesis. The pooled incidence of 30-day postoperative stroke was 10.6% (95% CI 7.0%-14.2%; p=.41, I2=3%). Pooled 30-day mortality was 4.9% (95% CI 2.0%-7.8%; p=.38, I2=7%). Combined early stroke/death was 15.7% (95% CI 11.2%-20.3%; p=.30, I2=15%). Subgroup analyses of 11 studies (without data missing) showed that a higher incidence of 30-day postoperative stroke was found in studies with aged participants (age≥71.3 years, p=.010), the higher percentage of COPD (≥30%, p= .011) and non-dissection-related pathologies (≥60.8%, p=.011). The higher 30-day postoperative mortality was found in studies with a high percentage of previous coronary artery disease (≥34.5%, p=.023). CONCLUSIONS: This review demonstrated that there were acceptable rates of 30-day postoperative stroke and death among patients undergoing inner branched TEVAR. It is strongly necessary to perform a rigorous risk assessment of aortic plaque embolism and coronary artery disease when the surgical plan of the inner branched TEVAR is determined. CLINICAL IMPACT: Treatment arch pathologies with inner branched TEVAR provides acceptable early stroke rate and mortality. Aortic pathology mainly influenced the early stroke rate, and early recognizing high-risk patients for aortic plaque embolism is of supreme importance for reducing the early stroke rate. In addition, the history of coronary artery disease was strongly associated with early mortality, and attention should be paid to the coronary artery assessment and perioperative management of these patients.

Association Between Aneurysm Wall Inflammation Detected by Imaging Perivascular Fat and Secondary Intervention Risk for Abdominal Aortic Aneurysm Patients After Endovascular Repair.

OBJECTIVE: To investigate the association between the imaging biomarker (volumetric perivascular characterization index [VPCI]) which indicates the aortic wall inflammation by mapping the spatial changes of perivascular fat attenuation on computed tomography angiography (CTA) and the reintervention risk for abdominal aortic aneurysm (AAA) patients after endovascular aortic repair (EVAR). METHODS: This case-control study included AAA patients undergoing EVAR from a single center (n=260). Cases were AAA patients undergoing reintervention after EVAR and a 1:1 frequency-matched control group of AAA patients post-EVAR with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up. The predictive variable (VPCI trajectory) was converted to binary variables according to the changing trend of VPCI with follow-up time. As a quasi-complete separation data pattern, least absolute shrinkage and selection operator (lasso) regression was used to screen and prove the VPCI trajectory as the best predictor, and the performance was evaluated by calculating the accuracy, sensitivity, and specificity. RESULTS: Between 2010 and 2021, 15 AAA patients after EVAR with type I/III endoleak, aneurysm rupture, or impending rupture were included. Compared with the 1:1 frequency-matched controls with a shrunken or ≥3-year stable sac and free of reintervention signs during the follow-up, VPCI trajectories of the case group were all upward trends, whereas the controls showed 86.7% downward trends (p<0.001). The best predictive model of lasso regressions included 4 variables, and VPCI trajectory was the most outstanding, followed by the proximal landing zone, the distal landing zone, and the infrarenal ß angle. The accuracy, sensitivity, and specificity of predicting the risk of reintervention were as follows, respectively: 93.3%, 100%, and 86.7%. CONCLUSIONS: The wall inflammation detected by imaging perivascular adipose tissue based on the CTAs was strongly associated with the reintervention risk for AAA patients after EVAR, which might hold major promise as a new imaging biomarker for the mechanism and treatment study of human AAAs before and after EVAR. CLINICAL IMPACT: The study introduces a novel imaging biomarker which indicates the aortic wall inflammation by mapping spatial changes of perivascular fat attenuation on CTA. This biomarker demonstrates a strong association with the reintervention risk in AAA patients after EVAR. Incorporation of VPCI into clinical practice has the potential to enhance the traditional surveillance methods (CT/CTAs) by providing clinicians with a non-invasive method to assess aortic wall inflammation and predict the risk of reintervention. Additionally, this study might offer a valuable tool for mechanism and treatment research in humans with AAAs both pre- and post-EVAR, ultimately improving patient outcomes and refining therapeutic strategies.

First-in-Human Clinical Trial of the WeFlow-JAAA Endograft System in Patients With Juxtarenal Abdominal Aortic Aneurysms.

OBJECTIVE: To preliminarily evaluate the safety and efficacy of the WeFlow-JAAA endograft, a novel off-the-shelf device designed for the repair of juxtarenal abdominal aortic aneurysms (JRAAAs) and pararenal abdominal aortic aneurysms (PRAAAs). METHODS: This prospective single-arm first-in-human clinical trial included patients with JRAAAs (infrarenal necks ≤10 mm) or PRAAAs with at least a 5 mm sealing zone below the superior mesenteric artery (SMA) who underwent endovascular repair using the WeFlow-JAAA endograft system. With this system, the celiac artery was addressed with a wide scallop, the renal arteries (RAs) were addressed with 2 standard inner branches, and the SMA was addressed with a "mini-inner-cuff" reinforced fenestration. The primary efficacy endpoint was the clinical success at 12 months. The primary safety endpoint was the freedom from major adverse events (MAEs) in the first 30 days after surgery. RESULTS: Fifteen patients (all men; mean age 68.5±6.0 years) were enrolled between October 2019 and August 2021. The median infrarenal neck length was 0 mm (IQR, 0-4 mm). Technical success was achieved in all patients. No MAEs occurred in the first 30 days. The mean fluoroscopy time was 73.1±27.8 minutes, and the mean volume of contrast media was 130.7±29.4 mL. Clinical success was maintained in all patients at 12 months. No aortic-related deaths, aneurysm rupture, type I or type III endoleak, or open surgery conversion occurred during the follow-up period. The secondary intervention was required only in 1 patient who developed an occluded right RA stent 14 months after the procedure. CONCLUSION: The WeFlow-JAAA endograft device appears to be safe and efficacious in selected patients with JRAAAs or PRAAAs with more than 5 mm sealing zone below SMA. Large-scale, multicenter, and prospective studies with long-term follow-ups are ongoing to validate our findings in China. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04745546 (URL: Guo's Visceral Arteries Reconstruction: The First in Man Study of WeFlow-JAAA Stent Graft System-Full-Text View-ClinicalTrials.gov). CLINICAL IMPACT: The first-in-human clinical trial of the WeFlow-JAAA endograft system demonstrates promising safety and efficacy in treating juxtarenal abdominal aortic aneurysms (JRAAAs) and partial pararenal abdominal aortic aneurysms (PRAAAs). This innovative off-the-shelf device offers a potential alternative to traditional endovascular aortic repair. The successful outcomes, including technical success in all patients, freedom from major adverse events, and maintenance of clinical success at 12 months, suggest a potential shift in clinical practice towards using the WeFlow-JAAA endograft system for selected patients. This study paves the way for larger-scale, multicenter, prospective studies to further validate its long-term safety and efficacy, offering clinicians a new option for managing complex abdominal aortic aneurysms.

Comparative Study of the Efficacy of Autologous Tooth Bone Powder and Inorganic Bovine Bone Powder on the Repair of Jaw Defects.

Context: The main pathological features of jaw cysts are bone defects. Obtaining autologous bone for transplantation repair has been associated with postoperative complications, and the amount of bone that dentist can collect is limited. Studies have found that autologous tooth bone powder is safe and has good bone-formation ability and stability. Objective: The study intended to examine the efficacy of implantation of autologous tooth bone powder and inorganic bovine bone powder, after marsupialization and second-stage curettage for large jaw cysts that dentist can't directly remove by surgery in clinical practice. Design: The research team designed a prospective randomized controlled trial. Setting: The study took place in the Head and Neck Surgery Department at Chongqing University Cancer Hospital in Chongqing, China. Participants: Participants were 60 patients at the hospital between 2016 and 2018 who had mandibular cysts that surgical operation couldn't directly remove by surgery in clinical practice. Intervention: At 4 months after curettage, the research team randomly divided participants into three groups: (1) an intervention group who received implants of autologous tooth bone powder into the bone defects, (2) a positive control group who received implants of inorganic bovine bone powder, and (3) a negative control group who received no implants of any material. Outcome Measures: The research team performed: (1) periodontal probing at a fixed anatomical point for the intervention and both control groups postintervention at one day and 4 months after surgery and recorded the changes in probing depth and (2) computed tomography (CT) scans at baseline one day before and postintervention at 4 months after the implantation to determine changes in the bone mineral density and compared them among the three groups. Results: The change in the height of the intervention group's fixed anatomical point postintervention at 4 months after surgery was significantly smaller than that of the positive control group (P < .05). In the CT scan analysis, the differences between the intervention and negative control groups and between the positive and negative control groups were statistically significant (P < .05); however, the difference between the intervention and positive control groups wasn't significant (P > .05). Conclusions: Autologous tooth bone powder and inorganic bovine bone powder can effectively repair bone defects caused by large jaw cysts and that the repaired effect may be better than that of spontaneous osteogenesis. The autologous tooth bone powder was associated with lower levels of bone loss than those seen with use of inorganic bovine bone powder.

[Impact of Endometriosis on the Therapeutic Effect of Hysteroscopic Fallopian Tube Catheterization Combined With Laparoscopy in Infertile Patients With Proximal Tubal Obstruction].

Objective: To investigate the impact of endometriosis on the therapeutic effect of hysteroscopic fallopian tube catheterization combined with laparoscopy in infertile patients with proximal tubal obstruction. Methods: We conducted a retrospective analysis of patients who underwent hysteroscopic fallopian tube catheterization combined with laparoscopy for infertility caused by proximal fallopian tube obstruction between January 19, 2016 and March 20, 2020 at the Department of Reproductive Endocrinology, West China Second Hospital, Sichuan University. During the operation, hydrotubation was performed to verify whether there was proximal tubal obstruction. Then, the patients were categorized into an endometriosis group and a non-endometriosis group according to whether their proximal tubal obstruction was combined with endometriosis. The baseline data were balanced by propensity score matching and the rate of successful surgical unblocking of proximal tubal obstruction in infertile patients by hysteroscopic fallopian tube catheterization combined with laparoscopy was calculated. Treating cases lost to follow-up in both groups as non-pregnant cases according to the principle of intention-to-treat analysis, we followed up the pregnancy outcomes after surgery. The primary indicators included overall successful surgical unblocking rate, clinical pregnancy rate, and spontaneous pregnancy rate, while the secondary indicators included live birth rate, miscarriage rate, ectopic pregnancy rate, and the mean time to spontaneous pregnancy after surgery. The primary indicators included overall successful surgical unblocking rate, clinical pregnancy rate, and spontaneous conception rate, while the secondary indicators included live birth rate, miscarriage rate, ectopic pregnancy rate, and the mean time to spontaneous pregnancy after surgery. Results: After propensity score matching, 113 cases were included in each of the two groups, with the overall successful surgical unblocking rate being 72.6%. The successful surgical unblocking rate of patients in the endometriosis group was higher than that of the non-endometriosis group, with the difference being statistically significant (78.8% vs. 66.4%, P<0.05). A total of 38 patients were lost after follow-up matching. Postoperative follow-up was performed to date and, through intention-to-treat analysis, the spontaneous conception rate was found to be higher in the endometriosis group than that in the non-endometriosis group (44.2% vs. 30.1%, P<0.05), while the mean time to spontaneous pregnancy after surgery was shorter in the endometriosis group than that in the non-endometriosis group (46 months vs. 53 months, P<0.05). There was no significant difference in clinical pregnancy rate, live birth rate, miscarriage rate, and ectopic pregnancy rate between the endometriosis group and the non-endometriosis group ( P>0.05). Conclusion: When infertility caused by proximal tubal obstruction is combined with endometriosis, performing hysteroscopic fallopian tube catheterization combined with laparoscopy contributes to the improvement of reproduction outcomes.

Long-Lived Multiple Charge Separation by Proton-Coupled Electron Transfer.

Multiple charge separation has been successfully realized by a proton-coupled electron transfer reaction in an organic cocrystal. Benefiting from the adjustable electronic energy level of the electron donor and acceptor through thermal-induced proton migration, distinct optical absorption behaviors combined with color changes to blue or green are observed in these charge-separated states. It is of interest to note that such charge-separated states exhibit a longer lifetime of over a month as a result of the excellent coplanarity and π-π interaction of the electron acceptors. Moreover, the enhanced absorption toward longer wavelengths endows the charge-separated state with near-infrared (808 nm) photothermal conversion for imaging and bacterial inhibition, whereby the conversion performance can be controlled by the degree of proton migration.

Inverted base composition skews and discontinuous mitochondrial genome architecture evolution in the Enoplea (Nematoda).

BACKGROUND: Within the class Enoplea, the earliest-branching lineages in the phylum Nematoda, the relatively highly conserved ancestral mitochondrial architecture of Trichinellida is in stark contrast to the rapidly evolving architecture of Dorylaimida and Mermithida. To better understand the evolution of mitogenomic architecture in this lineage, we sequenced the mitogenome of a fish parasite Pseudocapillaria tomentosa (Trichinellida: Capillariidae) and compared it to all available enoplean mitogenomes. RESULTS: P. tomentosa exhibited highly reduced noncoding regions (the largest was 98 bp), and a unique base composition among the Enoplea. We attributed the latter to the inverted GC skew (0.08) in comparison to the ancestral skew in Trichinellidae (-0.43 to -0.37). Capillariidae, Trichuridae and Longidoridae (Dorylaimida) generally exhibited low negative or low positive skews (-0.1 to 0.1), whereas Mermithidae exhibited fully inverted low skews (0 to 0.05). This is indicative of inversions in the strand replication order or otherwise disrupted replication mechanism in the lineages with reduced/inverted skews. Among the Trichinellida, Trichinellidae and Trichuridae have almost perfectly conserved architecture, whereas Capillariidae exhibit multiple rearrangements of tRNA genes. In contrast, Mermithidae (Mermithida) and Longidoridae (Dorylaimida) exhibit almost no similarity to the ancestral architecture. CONCLUSIONS: Longidoridae exhibited more rearranged mitogenomic architecture than the hypervariable Mermithidae. Similar to the Chromadorea, the evolution of mitochondrial architecture in enoplean nematodes exhibits a strong discontinuity: lineages possessing a mostly conserved architecture over tens of millions of years are interspersed with lineages exhibiting architectural hypervariability. As Longidoridae also have some of the smallest metazoan mitochondrial genomes, they contradict the prediction that compact mitogenomes should be structurally stable. Lineages exhibiting inverted skews appear to represent the intermediate phase between the Trichinellidae (ancestral) and fully derived skews in Chromadorean mitogenomes (GC skews = 0.18 to 0.64). Multiple lines of evidence (CAT-GTR analysis in our study, a majority of previous mitogenomic results, and skew disruption scenarios) support the Dorylaimia split into two sister-clades: Dorylaimida + Mermithida and Trichinellida. However, skew inversions produce strong base composition biases, which can hamper phylogenetic and other evolutionary studies, so enoplean mitogenomes have to be used with utmost care in evolutionary studies.

A systematic review and meta-analysis of real-world studies evaluating the association between beta-blocker use and postoperative adverse events of carotid endarterectomy.

OBJECTIVE: The objective of this study was to estimate the association of beta-blocker use with postoperative adverse events of carotid endarterectomy (CEA) based on real-world data. METHODS: Electronic bibliographic sources (MEDLINE, EMBASE, and CENTRAL) were searched up to April 2021 using a combination of thesaurus and free-text terms to identify the studies about the effect of beta-blockers on outcomes of CEA. The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All observational studies and randomized controlled trials investigating the effect of preoperative beta-blockers on the outcomes of CEA were included. Independent extraction of articles by two authors using predefined data fields, including study quality indicators. All pooled analyses were based on a random-effects model. RESULTS: A total of seven observational studies (six case-control studies and one cohort study) were included. Of the three case-control studies that examined the association of beta-blockers with composite postoperative adverse events, two studies including three datasets that totaled 24,161 participants were included in the quantitative synthesis, and the overall results showed a statistically significant association between beta-blocker use and composite postoperative adverse events of CEA (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.15-1.59; P = .0003; I2 = 13%). Publication bias was not present in the meta-analysis (Egger test showed nonsignificant results: P = .453). Two of the included studies utilized indirect measures of cerebral ischemia: intraoperative electroencephalograph, intraoperative hemodynamic indicators; and found a significant association between beta-blockers and intraoperative cerebral ischemia. Another two studies were included for meta-analysis on the association between beta-blockers and 30-day strokes or death of CEA (OR, 1.61; 95% CI, 0.98-2.65; P = .06; I2 = 0%). Of all included studies, there was only one cohort study that reported the association of beta-blockers with postoperative myocardial infarction by χ2 analysis (OR, 1.96; 95% CI, 1.86-2.07). CONCLUSIONS: This systematic review suggested that there was an increased risk of postoperative adverse outcomes of CEA among beta-blocker users compared with nonusers in the real world.

Synthesis of 2,2-Difluoro-3-hydroxy-1,4-diketones via an HFIP-Catalyzed Mukaiyama Aldol Reaction of Glyoxal Monohydrates with Difluoroenoxysilanes.

A novel efficient HFIP-catalyzed synthesis of structurally diverse 2,2-difluoro-3-hydroxy-1,4-diketone derivatives from readily available glyoxal monohydrates and difluoroenoxysilanes is described. This convenient protocol is induced by the distinctive fluorine effect of the reactants and the fluoroalcohol catalyst, which represents the first application of fluoroalcohol catalysis in a Mukaiyama aldol reaction.

Surfaxin attenuates PM2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke.

Epidemiologic studies have shown that the fine particulate matter 2.5 (PM2.5) exaggerates chronic airway inflammation involving in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Surfactant proteins (SPs) decreases significantly related to airflow limitation and airway inflammation. However, how to restore the reduction of SPs levels in airway inflammation exposed to PM2.5 has not been well understood. In the present study, the SPs including SPA, SPB, SPC and SPD levels in bronchoalveolar lavage fluid (BALF) were detected from patients with stable COPD. Rats were exposed to cigarette smoke and PM2.5. After given with Surfaxin, the expression of SPs, protein kinase C (PKC) and tight junction protein (ZO-1) in lung tissue and the levels of C-reactive protein (CRP) and fibrinogen (FIB) in plasma was observed. The results showed that SPA, SPB and SPD were significantly lower than those of the control group (p < 0.01). PM2.5 aggravated smoking-induced airway inflammation and oxidative stress demonstrated by pathological changes of lung tissue and increased levels of CRP and PKC in vivo. PM2.5 decreased the expression of all the SPs and ZO-1, which could be significantly restored by Surfaxin. These findings indicate that Surfaxin protects the alveolar epithelium from PM2.5 in airway inflammation through increasing SPs.

Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

OBJECTIVES: To investigate perioperative clinicopathological predictors and establish a predictive nomogram for survival in patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy. METHODS: Patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy were included in the study between January 2014 and June 2020. Cox regression analysis was used for univariate and multivariate survival analyses. A predictive nomogram for survival was established and internally validated using bootstrap resampling method. RESULTS: A total of 228 patients were enrolled in this study. The median age was 60 years (interquartile range 53-66 years), consisting of 174 (76.3%) males and 54 (23.7%) females. The median follow-up time was 17.5 months (range 1-74 months), 26.8% (61 of 228) patients died of all causes. In multivariable analysis, hemoglobin less than the lower limit of normal (hazard ratio 1.73; 95% confidence interval 1.01-2.96; P = 0.045), sarcomatoid feature (hazard ratio 3.67; 95% confidence interval 1.97-6.82; P < 0.001), perirenal fat invasion (hazard ratio 1.80; 95% confidence interval 1.05-3.09; P = 0.033), histological subtype (hazard ratio 2.74; 95% confidence interval 1.39-5.41; P = 0.004), and metastasis at surgery (hazard ratio 1.71; 95% confidence interval 1.01-2.90; P = 0.047) were independently associated with overall survival. The result of internal validation presented that the predictive performance of the nomogram for survival measured by C-index was 0.77. CONCLUSIONS: We developed a predictive nomogram with well-internal validation for survival in patients with renal cell carcinoma and venous tumor thrombus, which can greatly promote risk stratification and treatment planning.