Relationship between hepatic surgical margins of colorectal cancer liver metastases and prognosis: A review.

Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.

Diagnostic value of conventional endoscopic ultrasound for lymph node metastasis in upper gastrointestinal neoplasia: A meta-analysis.

BACKGROUND: Upper gastrointestinal neoplasia mainly includes esophageal cancer and gastric cancer, both of which have high morbidity and mortality. Lymph node metastasis (LNM), as the most common metastasis mode of both diseases, is an important factor affecting tumor stage, treatment strategy and clinical prognosis. As a new fusion technology, endoscopic ultrasound (EUS) is becoming increasingly used in the diagnosis and treatment of digestive system diseases, but its use in detecting LNM in clinical practice remains limited. AIM: To evaluate the diagnostic value of conventional EUS for LNM in upper gastrointestinal neoplasia. METHODS: Using the search mode of "MeSH + Entry Terms" and according to the predetermined inclusion and exclusion criteria, we conducted a comprehensive search and screening of the PubMed, EMBASE and Cochrane Library databases from January 1, 2000 to October 1, 2022. Study data were extracted according to the predetermined data extraction form. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool, and the results of the quality assessment were presented using Review Manager 5.3.5 software. Finally, Stata14.0 software was used for a series of statistical analyses. RESULTS: A total of 22 studies were included in our study, including 2986 patients. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic score and diagnostic odds ratio of conventional EUS in the diagnosis of upper gastrointestinal neoplasia LNM were 0.62 [95% confidence interval (CI): 0.50-0.73], 0.80 (95%CI: 0.73-0.86), 3.15 (95%CI: 2.46-4.03), 0.47 (95%CI: 0.36-0.61), 1.90 (95%CI: 1.51-2.29) and 6.67 (95%CI: 4.52-9.84), respectively. The area under the summary receiver operating characteristic curve was 0.80 (95%CI: 0.76-0.83). Sensitivity analysis indicated that the results of the meta-analysis were stable. There was considerable heterogeneity among the included studies, and the threshold effect was an important source of heterogeneity. Univariable meta-regression and subgroup analysis showed that tumor type, sample size and EUS diagnostic criteria were significant sources of heterogeneity in specificity (P < 0.05). No significant publication bias was found. CONCLUSION: Conventional EUS has certain clinical value and can assist in the detection of LNM in upper gastrointestinal neoplasia, but it cannot be used as a confirmatory or exclusionary test.

Oxytocin increases itch sensitivity of mice in late pregnancy and its peripheral receptor mechanism of itch-promoting effect.

Oxytocin (OXT) is secreted in a large amount during the middle and late pregnancy. Except for the regulation of functions related to childbirth, OXT is involved in the regulation of cognition, social behavior, addiction, pain and so on. Our aim is to confirm the increase of OXT content in mice in late pregnancy is the main cause of itch during pregnancy and observe whether exogenously administered OXT can induce or increase itch sensitivity. The research shows that itch sensitivity of mice increased significantly in late pregnancy and basically returned to normal one day after delivery. The number of OXT-positive neurons in paraventricular nucleus (PVN) and the content of OXT in serum of the late pregnant mice increased significantly, and decreased sharply after delivery. Intradermal injection of low concentration of OXT (0.2 nmol/L) could not induce scratching behavior in mice, but high concentration of OXT (5 nmol/L, 10 nmol/L) could do this in a dose-dependent manner. Low concentration of OXT significantly increased the itch sensitivity to histamine. Intradermal injection of oxytocin receptor (OXTR) or arginine vasopressin-1a receptor (AVPR1A) antagonist did not affect histamine-induced scratching behavior, but both reversed the increase of itch sensitivity in late pregnant mice or the facilitated itch sensitivity by OXT. Study suggests that both endogenous and exogenous increases in OXT can increase the body's sensitivity to itch, and even induce itch directly. Pruritus during pregnancy is closely related to the increase of OXT content in vivo. In the periphery, the itch-promoting effect of OXT is mediated by OXTR and AVPR1A.

Continuous carbon capture in an electrochemical solid-electrolyte reactor.

Electrochemical carbon-capture technologies, with renewable electricity as the energy input, are promising for carbon management but still suffer from low capture rates, oxygen sensitivity or system complexity1-6. Here we demonstrate a continuous electrochemical carbon-capture design by coupling oxygen/water (O2/H2O) redox couple with a modular solid-electrolyte reactor7. By performing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) redox electrolysis, our device can efficiently absorb dilute carbon dioxide (CO2) molecules at the high-alkaline cathode-membrane interface to form carbonate ions, followed by a neutralization process through the proton flux from the anode to continuously output a high-purity (>99%) CO2 stream from the middle solid-electrolyte layer. No chemical inputs were needed nor side products generated during the whole carbon absorption/release process. High carbon-capture rates (440 mA cm-2, 0.137 mmolCO2 min-1 cm-2 or 86.7 kgCO2 day-1 m-2), high Faradaic efficiencies (>90% based on carbonate), high carbon-removal efficiency (>98%) in simulated flue gas and low energy consumption (starting from about 150 kJ per molCO2) were demonstrated in our carbon-capture solid-electrolyte reactor, suggesting promising practical applications.

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation.

Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Non-iridium-based electrocatalyst for durable acidic oxygen evolution reaction in proton exchange membrane water electrolysis.

Iridium-based electrocatalysts remain the only practical anode catalysts for proton exchange membrane (PEM) water electrolysis, due to their excellent stability under acidic oxygen evolution reaction (OER), but are greatly limited by their high cost and low reserves. Here, we report a nickel-stabilized, ruthenium dioxide (Ni-RuO2) catalyst, a promising alternative to iridium, with high activity and durability in acidic OER for PEM water electrolysis. While pristine RuO2 showed poor acidic OER stability and degraded within a short period of continuous operation, the incorporation of Ni greatly stabilized the RuO2 lattice and extended its durability by more than one order of magnitude. When applied to the anode of a PEM water electrolyser, our Ni-RuO2 catalyst demonstrated >1,000 h stability under a water-splitting current of 200 mA cm-2, suggesting potential for practical applications. Density functional theory studies, coupled with operando differential electrochemical mass spectroscopy analysis, confirmed the adsorbate-evolving mechanism on Ni-RuO2, as well as the critical role of Ni dopants in stabilization of surface Ru and subsurface oxygen for improved OER durability.

Corticotropin-releasing factor is involved in acute stress-induced analgesia and antipruritus.

BACKGROUND: Under the condition of stress, the hypothalamic-pituitary-adrenal axis (HPA axis) is activated and causes the secretion of corticotropin-releasing factor (CRF). Previous studies have demonstrated that CRF is involved in the regulation of pain and itch. Thus, it remains worthy to explore whether the desensitization of pain and itch under high-intensity acute stress (such as high fear and tension) is related to the sharp increase of CRF. METHODS: Forced swimming was used to simulate acute stress. ELISA and pharmacological methods were conducted to observe the effects of forced swimming on acute pain or itch and the relationship between blood CRF content and itch or pain behavior. Intracerebroventricular (ICV) administration of CRF was conducted to examine the effects of CRF on acute pain or itch. Intrathecal administration of CRF receptor agonist or antagonist was conducted to examine the receptor mechanisms of the regulatory role of CRF in pain and itch. RESULTS: ELISA experiment showed that the serum CRF in mice reached its peak within 5-10 min after acute stress (forced swimming). Behavioral data showed that the scratching behavior induced by itch agents decreased after acute swimming, while the mechanical pain threshold increased significantly. The inhibitory effect of acute stress on pain and itch is mediated by CRF receptor2 (CRFR2). Then, ICV injection of CRF was used to simulate the massive release of CRF under acute stress, and we observed that the scratching behavior induced by histamine or chloroquine was significantly inhibited after ICV injection of CRF. The above effects of CRF are mainly mediated by CRFR2. These results suggest that 5-10 min after acute stress, a large amount of CRF is released into the blood from the hypothalamus, which significantly inhibits acute pain and itch by acting on CRFR2. ICV injection of CRF can replicate the antipruritus effects of acute stress. CONCLUSIONS: The present study investigated the mechanism of acute stress-induced analgesia and antipruritus and provided theoretical support for the treatment of pain and itch.

Changes in Gallbladder Contractile Function and its Influencing Factors After Minimally Invasive Gallbladder-Preserving Surgery for Cholecystitis With Incarcerated Gallstones.

Background: Cholecystitis with incarcerated gallstones (CIG) is a type of acute abdomen in the field of hepatobiliary surgery. Whether gallbladder-preserving surgery (GPS) can be performed to treat it, however, depends on the improvement of gallbladder contractile function. The present study aimed to investigate the changes in gallbladder contractile function and its influencing factors after minimally invasive GPS for CIG. Methods: A total of 95 patients with CIG treated in the Aerospace Center Hospital between May 2017 and May 2019 were enrolled as the study subjects. All patients received minimally invasive GPS. The patients' operation-related conditions (including stone removal success rate, duration of surgery, intraoperative blood loss, etc.), changes in gallbladder contractile function, and influencing factors of GPS were analyzed. Results: Among the 95 patients included in the study, the success rate of stone removal was 100%, the duration of surgery was 76.0 ± 26.5 min, and the intraoperative blood loss was 10.17 ± 4.43 ml. The rate of good gallbladder contractile function at one and two years after surgery was significantly higher than before surgery (P < 0.05). Age, duration of surgery, stone recurrence, and diabetes were the independent risk factors for postoperative gallbladder contractile function (P < 0.05). Conclusion: Minimally invasive GPS for patients with CIG has a good curative effect. The changes in gallbladder contractile function after the surgery are influenced by many factors.

Breast Cancer Recurrence after Smooth versus Textured Implant-Based Breast Reconstruction: A Matched Cohort Study.

BACKGROUND: An increasing number of reports on breast implant-associated anaplastic large-cell lymphoma have recently raised concerns about the potential influence of breast implants on carcinogenicity, particularly implants with a textured surface. The authors compared the recurrence outcomes between smooth and textured implant reconstructions for breast cancer. METHODS: All patients who underwent immediate direct-to-implant-based breast reconstruction for primary breast cancer between January of 2010 and December of 2016 were reviewed. A total of 590 patients were included. After propensity score 1:2 matching, 138 patients were included in the smooth implant group and 276 patients in the textured implant group. Locoregional recurrence-free survival, disease-free survival, and distant metastasis-free survival rates were compared between the groups. RESULTS: After matching, the median follow-up periods were 62 months and 66 months for the smooth and textured groups, respectively. The authors observed no significant differences between the smooth and textured implant groups in terms of locoregional recurrence (10.9 percent versus 11.6 percent; p = 0.827), distant metastasis (3.6 percent versus 4.0 percent; p = 0.547), or first recurrence (12.3 percent versus 13.4 percent; p = 0.757) rates. No significant differences were observed between the groups in 5-year locoregional recurrence-free survival (89.5 percent versus 89.4 percent; p = 0.840), disease-free survival (87.7 percent versus 88.1 percent; p = 0.794), or distant metastasis-free survival (98.8 percent versus 96.8 percent; p = 0.741) rates. CONCLUSIONS: No significant differences were observed between the smooth and textured implant groups in this matched cohort analysis of recurrence outcomes in patients with primary breast cancer who underwent immediate direct-to-implant reconstruction. Further larger scale investigations are necessary to validate the authors' results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Highly Efficient Oxygen Reduction Reaction Electro-Catalyzed by Ultrasmall Pt@Mn Core-Shell Nanoparticles.

Electro-catalyzed oxygen reduction reaction (ORR), as the positive electrode reaction, is significant to the performance of fuel cells and metal-air batteries. Toward ORR, ultra-small Pt@Mn core-shell nanoparticles catalysts supported on Ketjen black are synthesized by a simple one-pot hydrothermal method. TEM results show that the Pt@Mn/C nanoparticles with an average size of 3∼4 nm are uniformly distributed on the carbon surface. ORR performance of the electrocatalysts shows that Pt@Mn/C exhibits better oxygen reduction activity than Pt/C (20 wt %) in a KOH solution. Methanol tolerance ability as well as the durability of the Pt@Mn/C is also superior to the performance of Pt/C, suggesting an enhanced ORR activity upon the introduction of Mn.

Efficient conversion of low-concentration nitrate sources into ammonia on a Ru-dispersed Cu nanowire electrocatalyst.

Electrochemically converting nitrate ions, a widely distributed nitrogen source in industrial wastewater and polluted groundwater, into ammonia represents a sustainable route for both wastewater treatment and ammonia generation. However, it is currently hindered by low catalytic activities, especially under low nitrate concentrations. Here we report a high-performance Ru-dispersed Cu nanowire catalyst that delivers an industrial-relevant nitrate reduction current of 1 A cm-2 while maintaining a high NH3 Faradaic efficiency of 93%. More importantly, this high nitrate-reduction catalytic activity enables over a 99% nitrate conversion into ammonia, from an industrial wastewater level of 2,000 ppm to a drinkable water level <50 ppm, while still maintaining an over 90% Faradaic efficiency. Coupling the nitrate reduction effluent stream with an air stripping process, we successfully obtained high purity solid NH4Cl and liquid NH3 solution products, which suggests a practical approach to convert wastewater nitrate into valuable ammonia products. Density functional theory calculations reveal that the highly dispersed Ru atoms provide active nitrate reduction sites and the surrounding Cu sites can suppress the main side reaction, the hydrogen evolution reaction.

Electrochemical oxygen reduction to hydrogen peroxide at practical rates in strong acidic media.

Electrochemical oxygen reduction to hydrogen peroxide (H2O2) in acidic media, especially in proton exchange membrane (PEM) electrode assembly reactors, suffers from low selectivity and the lack of low-cost catalysts. Here we present a cation-regulated interfacial engineering approach to promote the H2O2 selectivity (over 80%) under industrial-relevant generation rates (over 400 mA cm-2) in strong acidic media using just carbon black catalyst and a small number of alkali metal cations, representing a 25-fold improvement compared to that without cation additives. Our density functional theory simulation suggests a "shielding effect" of alkali metal cations which squeeze away the catalyst/electrolyte interfacial protons and thus prevent further reduction of generated H2O2 to water. A double-PEM solid electrolyte reactor was further developed to realize a continuous, selective (∼90%) and stable (over 500 hours) generation of H2O2 via implementing this cation effect for practical applications.

CO2/carbonate-mediated electrochemical water oxidation to hydrogen peroxide.

Electrochemical water oxidation reaction (WOR) to hydrogen peroxide (H2O2) via a 2e- pathway provides a sustainable H2O2 synthetic route, but is challenged by the traditional 4e- counterpart of oxygen evolution. Here we report a CO2/carbonate mediation approach to steering the WOR pathway from 4e- to 2e-. Using fluorine-doped tin oxide electrode in carbonate solutions, we achieved high H2O2 selectivity of up to 87%, and delivered unprecedented H2O2 partial currents of up to 1.3 A cm-2, which represents orders of magnitude improvement compared to literature. Molecular dynamics simulations, coupled with electron paramagnetic resonance and isotope labeling experiments, suggested that carbonate mediates the WOR pathway to H2O2 through the formation of carbonate radical and percarbonate intermediates. The high selectivity, industrial-relevant activity, and good durability open up practical opportunities for delocalized H2O2 production.

Impact of Local Breast Cancer Recurrence on Reconstructed Breast in Nipple-Sparing Mastectomy with Immediate Reconstruction.

The impact of locally recurrent breast cancer on reconstructed breasts remains largely unknown. Therefore, this study aimed to investigate the incidence of reconstruction loss due to local recurrence in patients who underwent nipple-sparing mastectomy with immediate reconstruction for breast cancer and to identify potential recurrence-associated risk factors for loss of index reconstruction. The records of 1,696 patients who underwent nipple-sparing mastectomy with immediate reconstruction between March 2003 and December 2016 at a single institution were reviewed. Among them, 128 patients with local breast cancer recurrence as the first event were analyzed. The primary outcome was loss of reconstruction due to local breast cancer recurrence. Reconstruction loss was classified as partial flap loss with breast distortion, complete flap loss, or implant loss during salvage treatment of local recurrence. Reconstruction loss occurred in 21 of the 128 patients (16%). Reconstruction loss rates were 20% for autologous and 9.5% for implant-based reconstruction (P = 0.204). Multivariate analysis showed that recurrent tumor size > 2.0 cm and multifocal recurrence were independent factors associated with an increased risk of reconstruction loss. Moreover, age ≥ 50 years at the time of recurrence diagnosis, recurrent tumor size > 2.0 cm, and multifocal recurrence were independently associated with complete flap/implant loss in the multivariate analysis. The incidence of reconstruction loss due to local breast cancer recurrence after nipple-sparing mastectomy with immediate reconstruction was low in this study. Age ≥ 50 years at recurrence diagnosis and the extent of local recurrence independently affected reconstruction loss. To detect recurrence early, careful follow-up through regular ultrasonography or magnetic resonance imaging at the reconstruction site is important.

Minimal change disease associated with gastrointestinal stromal tumor accompanied by significantly elevated serum IgE level: a case report.

BACKGROUND: Minimal change disease (MCD) is a common cause of the nephrotic syndrome. Several studies have shown an increased incidence of cancer in patients with MCD. However, there are no reports on the association between MCD and gastrointestinal stromal tumor (GIST). CASE PRESENTATION: We report a case of a 66-year-old female with severe nephrotic syndrome and concomitant duodenal GIST. Immunoglobulin test showed a significant increase of IgE levels. The diagnosis of renal histopathology was MCD with subacute tubulointerstitial injury. The combination of preoperative Imatinib mesylate chemotherapy and tumor excision was accompanied by significant remission of proteinuria, and IgE level decreasing, without immunosuppressivetherapy. CONCLUSIONS: It is the first case report that MCD was associated with GIST and elevated IgE level. Clinically, in patients with elevated IgE level associated with nephrotic syndrome, the possibility of tumor must be taken into account when allergic factors are excluded.

The patterns and spatial locations of local recurrence in breast cancer with implant-based reconstruction after mastectomy.

BACKGROUND AND PURPOSE: The European Society for Radiotherapy and Oncology (ESTRO) recently defined delineation guidelines for the clinical target volume for postmastectomy radiation therapy (PMRT) after immediate implant-based reconstruction for early-stage breast cancer. We analyzed the three-dimensional location and pattern of local recurrence in accordance with the reconstruction type and ESTRO-target volume. MATERIALS AND METHODS: This retrospective study involved patients who had undergone mastectomy with implant reconstruction between 2010 and 2019 and who had local recurrence as the first event. For mapping analysis, one subpectoral and one prepectoral implant patient were selected. All recurrence lesions were contoured and mapped in a representative case. RESULTS: A total of 1327 patients with breast cancer who underwent mastectomy and implant-based breast reconstruction were identified; 51 were enrolled with a total of 65 lesions. In subpectoral implant patients, 93% of recurrences were located in the ESTRO-target volume. No recurrence occurred in the implant pocket, but 7% of the recurrent tumors developed in the pectoralis major and deep thoracic muscle. In prepectoral implant patients, all recurrent tumors occurred within the ESTRO-target volume. CONCLUSION: The ESTRO-target volume in PMRT after reconstruction encompassed most local recurrences in patients who underwent mastectomy with immediate implant reconstruction. Our results support the application of the ESTRO Advisory Committee for Radiation Oncology Practice consensus guideline for target volume of PMRT after immediate implant-based reconstruction for early-stage breast cancer.

Molecular typing of familial temporal lobe epilepsy.

The pathogenesis of temporal lobe epilepsy (TLE) was originally considered to be acquired. However, some reports showed that TLE was clustered in some families, indicating a genetic etiology. With the popularity of genetic testing technology, eleven different types of familial TLE (FTLE), including ETL1-ETL11, have been reported, of which ETL9-ETL11 had not yet been included in the OMIM database. These types of FTLE were caused by different genes/Loci and had distinct characteristics. ETL1, ETL7 and ETL10 were characterized by auditory, visual and aphasia seizures, leading to the diagnosis of familial lateral TLE. ETL2, ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities, indicating a mesial temporal origin. Febrile seizures were common in FTLEs such as ETL2, ETL5, ETL6 and ETL11. ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura. Considering the diversity and complexity of the symptoms of TLE, neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully. Most FTLE patients had a good prognosis with or without anti-seizure medication treatment, with the exception of patients with heterozygous mutations of the CPA6 gene. The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development, differentiation and synaptic signaling. In this article, we describe the research progress on eleven different types of FTLE. The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.

Study on painless gastroscopy and POCD of smoking patients under general anesthesia.

The number of smoking patients receiving anesthesia and surgical treatment is increasing day by day. It will be useful for medical advancement to explore whether smoking is an independent risk factor for postoperative cognitive impairment. A double-blind, parallel, and controlled study was conducted on 112 patients who fulfilled the criteria for inclusion in this study and planned to undergo painless gastroscopy under general anesthesia. The baseline mini-mental state examination (MMSE) scores and basic information were collected. The changes in the MMSE scores after waking up and 3 days after anesthesia were observed, and the adverse events (respiratory adverse reactions, circulatory fluctuations, and adverse reactions, drug use, etc.) were analyzed by logistic regression. The baseline level of each group is consistent, which is worth studying. The MMSE score of the smoking group after anesthesia was significantly different from that of the control group (p < 0.05), but there was no significant difference between the two groups 3 days after anesthesia. Among them, the differences in adverse events between the two groups were in terms of hiccup, postoperative cough, and SpO2 < 90% (p < 0.05). Regression analysis indicates that smoking after anesthesia leads to the occurrence of postoperative cough. Smoking is probably an independent risk factor for post-operative cognitive dysfunction (POCD) in early postoperative patients.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats.

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Oncologic outcomes of immediate breast reconstruction in young women with breast cancer receiving neoadjuvant chemotherapy.

BACKGROUND: Oncologic safety of postmastectomy breast reconstruction in young women with breast cancer is not well-defined, especially in the setting of neoadjuvant chemotherapy (NACT). We retrospectively compared the oncologic outcomes following nipple-sparing (NSM)/skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) and conventional mastectomy (CM) alone in young breast cancer patients after NACT. METHODS: A total of 1266 women with primary breast cancer who underwent NACT followed by total mastectomy with or without IBR were reviewed. Of these, only young patients (age ≤ 40 years at diagnosis) were included in the outcome analysis (n = 375). After propensity score-matching by clinical T and N stage, molecular subtype, response to NACT, and adjuvant radiotherapy status, 228 patients were 1:1 matched, comprising balanced IBR group (with NSM/SSM) and CM-alone group. RESULTS: The 5-year locoregional recurrence-free, disease-free, distant metastasis (DM)-free, and breast cancer-specific survival (BCSS) rates for the entire cohort of young patients were 83.4%, 65.3%, 71.7%, and 85.4%, respectively. Locoregional recurrence rates between the matched groups were similar (14% vs. 15.8%; p = 0.710); however, IBR group had significantly lower DM rate (27.2% vs. 40.4%; p = 0.036) and breast cancer mortality (14.9% vs. 27.2%; p = 0.023) than CM-alone group. IBR group showed significantly improved 5-year DM-free survival (74.1% vs. 62.6%; p = 0.043) and BCSS (89.1% vs. 77.6%; p = 0.048) rates than CM-alone group. CONCLUSIONS: Our results indicated that IBR with NSM/SSM does not negatively affect long-term oncologic outcomes compared to CM alone in young women with breast cancer receiving NACT.