NPAS4 Exacerbates Pyroptosis via Transcriptionally Regulating NLRP6 in the Acute Phase of Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11. In this study, we found that NPAS4 was upregulated in human and mouse peri-hematoma brain tissues and peaked at approximately 24 h after ICH modeling. Additionally, NPAS4 knockdown improved neurologic dysfunction and brain damage induced by ICH in mice after 24 h. Meanwhile, inhibiting NPAS4 expression reduced the levels of myeloperoxidase (MPO)-positive cells and Caspase-1/TUNEL-double-positive cells and decreased cleaved Caspase-1, cleaved Caspase-11, and N-terminal GSDMD levels. Consistently, NPAS4 overexpression reversed the above alternations after ICH in the mice. Moreover, NPAS4 could interact with the Nlrp6 promoter region (-400--391 bp and -33--24 bp) and activate the transcription of Nlrp6. Altogether, our study demonstrated that NPAS4, as a transcription factor, can exacerbate pyroptosis and transcriptionally activate NLRP6 in the acute phase of intracerebral hemorrhage in mice.

MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer.

Although targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly prolonged survival time and improved patients' quality of life, drug resistance has gradually emerged. This study explored the mechanisms underlying the effect of the motor neuron and pancreatic homeobox 1 (MNX1) genes on drug sensitivity in HER2-positive breast cancer. From July 2017 to 2018, core needle biopsies of HER2-positive breast cancer were collected from patients who received paclitaxel, carboplatin, and trastuzumab neoadjuvant therapy at our center. Based on treatment efficacy, 81 patients were divided into pathological complete response (pCR) and non-pCR groups. High-throughput RNA sequencing results were analyzed along with the GSE181574 dataset. MNX1 was significantly upregulated in the pCR group compared with the non-pCR group in both sequencing datasets, suggesting that MNX1 might be correlated with drug sensitivity in HER2-positive breast cancer. Meanwhile, tissue array results revealed that high MNX1 expression corresponded to a good prognosis. In vitro functional tests showed that upregulation of MNX1 significantly increased the sensitivity of HER2-positive breast cancer cells to lapatinib and pyrotinib. In conclusion, MNX1 may serve as a prognostic marker for patients with HER2-positive breast cancer, and its expression may facilitate clinical screening of patients sensitive to anti-HER2-targeted therapy.

Long-term recurrence-free survival and complications of percutaneous balloon compression and radiofrequency thermocoagulation of Gasserian ganglion for trigeminal neuralgia: A retrospective study of 1313 cases.

OBJECTIVE: To estimate long-term recurrence, complications after percutaneous balloon compression (PBC) and radiofrequency thermocoagulation (RFT) of gasserian ganglion among a large sample of patients with trigeminal neuralgia (TN) during a long-term follow-up. METHODS: A retrospective analysis of 1313 patients undergoing PBC or RFT for the treatment of TN was conducted from 2006 to 2020. Recurrence-free survival (RFS) was assessed by the Kaplan-Meier method. Complications including facial numbness, corneal reflex decrease and masseter weakness were also estimated. RESULTS: For patients who received first initial PBC and RFT, the median RFS was 130.1 months (95% CI: 124.4, 135.9) and 123.3 months (95% CI: 117.6, 128.9) in PBC and RFT group with log-rank p = 0.108. The RFS rate was, respectively, 90.6% (95% CI: 88.1%-93.3%) and 91.4% (95% CI: 89.1%-93.7%) at 1 year, 84.6% (95% CI: 81.4%-87.8%) and 83.3% (95% CI: 80.3%-86.3%) at 3 years, 81.5% (95% CI: 78.1%-85.0%), and 78.6% (95% CI: 75.2%-81.9%) at 5 years, 71.5% (95% CI: 67.5%-75.5%), and 64.8% (95% CI: 61.0%-68.7%) at 10 years in two groups. No significant difference was observed in facial numbness degree between two groups after procedure. Compared with PBC group, ophthalmic complication prevalence was higher in RFT group (9.6%) (p = 0.001). However, masseter weakness incidence was lower (10.7%) than that in PBC group (24.0%) with p < 0.001. CONCLUSIONS: Patients with TN seemed to attain similar long-term benefit from PBC and RFT, especially in elderly. However, in order to reduce postoperative complications, PBC provided a safer and alternative for treating TN involving ophthalmic division, whereas RFT could be employed as a preferred regimen for maxillary and mandibular TN.

Masticatory Dysfunction After Computed Tomography-Guided Plasma Ablation vs. Radiofrequency Ablation on Gasserian Ganglion for Idiopathic Trigeminal Neuralgia: A Randomized Controlled Trial.

OBJECTIVE: We aimed to evaluate masticatory dysfunction after two different types of ablation on the Gasserian ganglion for the treatment of idiopathic trigeminal neuralgia. We hypothesized that low-temperature plasma radiofrequency ablation (LTP-RFA) was noninferior to radiofrequency thermocoagulation (RFT) with respect to initial efficacy. METHODS: In the randomized, single-blind, parallel-group, noninferiority trial, 204 participants with idiopathic trigeminal neuralgia were randomly allocated to receive plasma ablation in the LTP-RFA group and radiofrequency ablation in the RFT group in a 1:1 ratio, with random block sizes of four or six. Participants were examined at baseline (T0), on the day of discharge (T1), and at the 6-month follow-up (T2). The primary end point was the clinincal effective rate in the LTP-RFA group compared with that in the RFT group after intervention on the day of discharge. Noninferiority was prespecified at -10%. RESULTS: The intention-to-treat analysis revealed that the initial efficacy rates were 91.2% in LTP-RFA group and 93.1% in RFT group (rate ratio [RR] = 0.979, 95% confidence interval [CI]: 0.904-1.061, P = 0.795). The difference between the two groups was 1.9% (95% CI: -5.6% to 9.4%), which showed that LTP-RFA demonstrated noninferiority compared with RFT in initial efficacy. Compared with the RFT group, the LTP-RFA group exhibited a significantly greater improvement in the maximum voltage of the masseter muscles with mean differences of 11.40 (95% CI: 10.52 to 12.27, P < 0.001) at T1 and 17.41 (95% CI: 14.68 to 20.13, P < 0.001) at T2, respectively. Similar results were observed for the asymmetry index of occlusion, the maximum voltage of the anterior temporalis, and the activity index of anterior temporalis / masseter muscles. No serious adverse events were observed in either group. CONCLUSIONS: Compared with the RFT group, noninferior efficacy for pain relief and improvement of masticatory function was revealed in the LTP-RFA group.

Factors Associated With Long-Term Risk of Recurrence After Percutaneous Radiofrequency Thermocoagulation of the Gasserian Ganglion for Patients With Trigeminal Neuralgia Involving the Ophthalmic Division: A Retrospective Study.

OBJECTIVE: To evaluate risk factors associated with recurrence after radiofrequency thermocoagulation (RFT) of the gasserian ganglion among patients with ophthalmic trigeminal neuralgia (TN) and prognostic factors in terms of recurrence-free survival (RFS) during a long-term follow-up. METHODS: From January 2005 to December 2017, 300 patients with ophthalmic TN underwent RFT. A retrospective analysis of 14-year outcomes was performed. Kaplan-Meier analysis was used for RFS after the procedure. Univariate and multivariate Cox regression analyses were performed to identify risk factors for pain recurrence. RESULTS: The initial effective rate of RFT for ophthalmic TN was 92%. The mean follow-up time was 77.38 ± 43.24 months. The cumulative probability of RFS was 86.94% at 1 year, 80.03% at 2 years, 77.27% at 3 years, 74.01% at 5 years, and 59.92% at 10 years after RFT. The mean duration of RFS was 114.67 months (95% confidence interval [CI] 106.27 to 123.06 months). In multivariate analysis, atypical pain (hazard ratio [HR] = 2.831, 95% CI 1.759 to 4.554, P < 0.001) and mild facial hypesthesia (HR = 2.540, 95% CI 1.309 to 4.931, P = 0.006) before RFT were independently associated with pain recurrence. Patients with a prognostic index (PI) > 1.27 were at high risk for pain recurrence. Major complications included troublesome dysesthesia (0.7%), keratitis (10.9%), diplopia (0.4%), facial paresthesia (6.2%), and masseter weakness (12.7%). Masseter weakness was more common in patients with V3 branch involvement. Three patients lost their sight due to keratitis. CONCLUSION: Our study investigated long-term outcomes and complications of RFT for ophthalmic TN. Patients at high risk for pain recurrence were identified, which might provide a basis for clinical decision making before RFT.

Factors Predicting Successful Outcomes for Percutaneous Radiofrequency Thermocoagulation in Patients With Idiopathic Trigeminal Neuralgia: Implications for Surgical Decision Making.

OBJECTIVES: In this study we aimed to identify specific factors predicting successful outcomes after percutaneous radiofrequency thermocoagulation (RFT) for idiopathic trigeminal neuralgia (ITN) and risk factors that were associated with inferior outcomes. METHODS: We retrospectively reviewed our cohort of 1,624 patients who underwent RFT for trigeminal neuralgia between January 2000 and December 2017. Demographic and clinical data including age, gender, disease duration, affected side, baseline pain score, pain distribution, history of previous surgical intervention, and pain characteristics were collected and evaluated for their association with outcome using univariate and multivariate logistic regression analysis. RESULTS: 78.1% of patients experienced a successful outcome of RFT for ITN as predefined criteria. Pain characteristics and history of surgical treatment were significant predictors associated with successful outcomes in regression analysis. Multivariate analysis identified provoked episodic pain at diagnosis (odds ratio [OR] = 23.629, 95% confidence interval [CI]: 16.316 to 34.219, P = 0.010), mixed pain (OR = 8.394, 95% CI: 5.951 to 11.840, P = 0.011), and no history of surgical treatment (OR = 2.189, 95% CI: 1.411 to 3.396, P = 0.019) as independent predictors for successful RFT outcome. CONCLUSION: Presence of provoked episodic pain and mixed pain were significantly associated with successful outcome of RFT for ITN. Moreover, patients with ITN who underwent RFT for the first time were more likely to benefit from successful outcome. These findings should be considered when managing ITN with RFT to improve the likelihood of a successful outcome.

Ultrasound-Guided Cervical Nerve Root Block for the Treatment of Acute Cervical Herpes Zoster: A Randomized Controlled Clinical Study.

OBJECTIVES: To evaluate the efficacy and safety of ultrasound-guided cervical nerve root block (CRB) on acute pain and its preventive effects on post-herpetic neuralgia (PHN) in patients with cervical herpes zoster (HZ). METHODS: 140 recruited participants were randomized 1:1 to receive ultrasound-guided CRB with either mixed drug liquid (treatment group) or similar looking placebo (placebo group). All patients received a 7-day course of oral antiviral treatment, pregabalin, and analgesics as needed. The primary efficacy was assessed on the basis of HZ burden of illness (HZ-BOI) scores over 30 days (BOI-30AUC ). Secondary outcomes included HZ-BOI scores through 30 to 90 days (BOI-30-90AUC ) and 90 to 180 days (BOI-90-180AUC ), quality of life (QoL) outcomes, concomitant analgesic consumption, and the incidence of PHN. Adverse events were recorded to evaluate safety. RESULTS: The BOI-30AUC values were 92.55 and 112.72 for the treatment and placebo groups, respectively (P < 0.01). Both the BOI-30-90AUC and BOI-90-180AUC in the treatment group were lower than those in the placebo group (P < 0.01). The incidence of PHN at 90 days was significantly less than that at 180 days in the treatment group (P = 0.036). A better improvement in QoL was found in the treatment group (P < 0.05). There was a greater decrease in analgesic use in the treatment group as compared to the placebo group (P < 0.05). No serious adverse events were observed. CONCLUSIONS: Ultrasound-guided CRB represented an early intervention and preventive strategy to reduce the BOI due to acute HZ in the cervical dermatome region, and might be feasible to reduce the incidence of PHN.

Application of Antidromic Conduction Monitoring in Ganglion Radiofrequency Thermocoagulation for Locating Trigeminal Branches in Trigeminal Neuralgia.

OBJECTIVE: The aim of this study was to investigate whether antidromic conduction monitoring (ACM) can be utilized to map the trigeminal system under sedation as a potential substitute for subjective paresthesia description (SPD) during percutaneous ganglion radiofrequency thermocoagulation (PGRT). METHODS: Eighty-two patients with 152 pain divisions of trigeminal neuralgia (TN) were treated by computed tomography (CT)-guided PGRT. After the puncture needle entered the foramen ovale (FO), sensory and motor stimulation were applied to locate the pain division. And the corresponding voltage values were recorded by patients' SPD. In the following, the proper location was certified by ACM. The corresponding earliest waves and voltage values in the identified trigeminal branch were also recorded to outline a comparison between two methods. RESULTS: The correlation of ACM and patients' SPD with voltage at ≤ 0.5 V was statistically significant (P < 0.05, r = 0.159; Spearman's rank correlation analysis). Although ACM and SPD showed weak correlation, as their interclass correlation coefficient was significant (F = 1.868, P < 0.01) with coefficient of internal consistency. Moreover, the two methods had consistency. Kruskal-Wallis test showed that ophthalmic (V1), maxillary (V2), and mandibular (V3) divisions had significant differences for test sensitivity (H = 15.945, P < 0.01). For comparison of sensitivities with ACM, V3 was most sensitive followed by V2 and then V1. CONCLUSION: ACM could potentially substitute for SPD of the paresthesias intra-operatively, enabling greater specificity and eliminating the need to interrupt the administration of anesthetic. These improvements would increase patient satisfaction and practitioner efficiency and accuracy.

Masticatory Muscles Dysfunction after CT-guided Percutaneous Trigeminal Radiofrequency Thermocoagulation for Trigeminal Neuralgia: A Detailed Analysis.

OBJECTIVE: The aim of this study was to investigate the severity and the natural course of masticatory muscles weakness that developed after CT-guided percutaneous trigeminal radiofrequency thermocoagulation (PT-RFT) for the treatment of idiopathic trigeminal neuralgia (ITN). METHODS: Twenty-seven patients with ITN were treated by CT-guided percutaneous trigeminal radiofrequency thermocoagulation. Each patients' occlusal function and surface electromyographic (sEMG) activity of the ipsilateral anterior temporalis (TA) and masseter muscles (MM) at mandibular postural position (MPP), and during a fast maximum voluntary clenching (MVC) from MPP to intercuspal position (ICP), were simultaneously recorded by the T-Scan III system and Bio-pak sEMG III system before (baseline), 3 days, 3 months, and 12 months after procedure. The incidence, degree, and prognosis of masticatory muscles dysfunction related to trigeminal nerve motor-branch injury were analyzed. RESULTS: Three days and 3 months after procedure, both the occlusal symmetry and the sEMG activity of ipsilateral TA and MM became significantly decreased compared to the baseline (P < 0.05). However, they demonstrated a gradual improvement toward preoperative values in follow-up, returning to complete in 23 patients at 12 months after procedure. None reported permanent masticatory paralysis. Pain relief was most significant on the third day after procedure. At the final clinical visit, a pain-free status was observed in 25 patients (92.6%). Meanwhile, the intensity of facial dysesthesia was mildest, whereas there were statistic differences compared with baseline. CONCLUSION: CT-guided PT-RFT for ITN remains an effective and safe surgical procedure, but there is a high rate of temporary masticatory dysfunction during a short time after procedure, appearing to be reversible in a period of 12 months.

Comparing long-term prognosis following different surgical methods in patients with early stage breast cancer and obesity: a retrospective cohort study in China.

OBJECTIVE: Breast-conserving therapy (BCT) includes breast-conserving surgery (BCS) combined with radiation therapy (RT). RT plays a crucial role in improving the prognosis of patients who undergo BCS. However, obesity is a potential risk factor for resistance to radiation. The aim of this study was to evaluate any difference in the long-term prognosis of patients with early stage breast cancer and obesity treated with BCT or total mastectomy (TM). DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study involving 1125 patients diagnosed with early stage breast cancer and obesity at the Shanghai Cancer Center of Fudan University from 2013 to 2016. OUTCOME MEASURES: Obesity in the Chinese population was defined as a body mass index ≥28 kg/m2. Surgical options included BCT and TM. The primary survival outcomes were overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). Inverse probability of treatment weighting (IPTW) was used to control for the impact of confounding factors on prognosis. RESULTS: The median follow-up times in the BCT group and TM group without postoperative RT were 51.1 months (IQR of 40.6-68.1 months) and 61.8 months (IQR of 46.5-76.7 months), respectively. After IPTW, the baseline data were balanced. Compared with those in the TM cohort, patients in the whole IPTW cohort in the BCT cohort had worse DFS (HR 4.280, 95% CI 2.180 to 8.400; p<0.001), RFS (HR 4.380, 95% CI 2.370 to 8.120; p<0.001) and OS (HR 3.590, 95% CI 1.620 to 7.950; p=0.002). CONCLUSION: In patients with early stage breast cancer and obesity, TM is associated with better survival outcomes than BCT.

Impact of obesity on sentinel lymph node biopsy outcomes and survival in breast cancer patients: A single-center retrospective study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early-stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. METHODS: Between 2013 and 2016, 7062 early-stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early-stage BC patients who had undergone SLNB. RESULTS: No significant association was observed between obesity and positive SLN rate in early-stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27-3.95, p = 0.005) and disease-free survival (HR 1.750, 95% CI 1.16-2.62, p = 0.007) were poorer in patients with high BMI. CONCLUSION: Obesity is an independent prognostic factor for early-stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate.

Paeoniflorin improves ulcerative colitis via regulation of PI3K­AKT based on network pharmacology analysis.

Paeoniflorin (PF) is the primary component derived from Paeonia lactiflora and white peony root and has been used widely for the treatment of ulcerative colitis (UC) in China. UC primarily manifests as a chronic inflammatory response in the intestine. In the present study, a network pharmacology approach was used to explore the specific effects and underlying mechanisms of action of PF in the treatment of UC. A research strategy based on network pharmacology, combining target prediction, network construction, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking simulation was used to predict the targets of PF. A total of 288 potential targets of PF and 599 UC-related targets were identified. A total of 60 therapeutic targets of PF against UC were identified. Of these, 20 core targets were obtained by protein-protein interaction network construction. GO and KEGG pathway analyses showed that PF alleviated UC through EGFR tyrosine kinase inhibitor resistance, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. Molecular docking simulation showed that AKT1 and EGFR had good binding energy with PF. Animal-based experiments revealed that the administration of PF ameliorated the colonic pathological damage in a dextran sulfate sodium-induced mouse model, resulting in lower levels of proinflammatory cytokines including IL-1ß, IL-6, and TNF-α, and higher levels of IL-10 and TGF-ß. PF decreased the mRNA and protein expression levels of AKT1, EGFR, mTOR, and PI3K. These findings suggested that PF plays a therapeutic protective role in the treatment of UC by regulating the PI3K/AKT signaling pathway.

CRTAM promotes antitumor immune response in triple negative breast cancer by enhancing CD8+ T cell infiltration.

The immunomodulatory (IM) subtype of triple negative breast cancer (TNBC) exhibits high expression of immune cell signaling genes and is more responsive to immunotherapy. However, the specific mechanism underlying this phenomenon remains unclear. One of the potential key genes appears to be the cytotoxic and regulatory T cell molecule (CRTAM). A cohort of 360 previously untreated TNBC patients from Fudan University Shanghai Cancer Center (FUSCC) underwent RNA sequencing analysis of their primary tumor tissue. Combined with three RNA-seq datasets obtained from the GEO database, a LASSO regression analysis was conducted to identify genes specific to the IM type of TNBC. Our findings revealed elevated CRTAM expression in the IM-type TNBC, which correlated with a favorable overall survival and recurrence-free survival in TNBC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated a strong association between CRTAM and immune responses as well as immune system processes. Notably, CRTAM overexpression induced STAT1 phosphorylation and upregulation of interferon-stimulated genes. We also found that CRTAM enhanced tumor-associated immune cell infiltration, especially CD8+ T cells, which may be related to the increased expression of MHC class I molecules caused by CRTAM overexpression. These results suggest that CRTAM may serve as a potential biomarker for predicting the efficacy of immunotherapy in TNBC.

Ferroptosis: Promising approach for cancer and cancer immunotherapy.

Ferroptosis is the cell death induced by ferrous ions and lipid peroxidation accumulation in tumor cells. Targeting ferroptosis, which is regulated by various metabolic and immune elements, might become a novel strategy for anti-tumor therapy. In this review, we will focus on the mechanism of ferroptosis and its interaction with cancer and tumor immune microenvironment, especially for the relationship between immune cells and ferroptosis. Also, we will discuss the latest preclinical progress of the collaboration between the ferroptosis-targeted drugs and immunotherapy, and the best potential conditions for their combined use. It will present a future insight on the possible value of ferroptosis in cancer immunotherapy.

Development of Sustainable Engineered Cementitious Composites by Incorporating Local Recycled Fine Aggregate.

In this study, sustainable engineered cementitious composites (ECC) exhibiting high tensile strength as well as high tensile strain capacity were successfully developed by incorporating polyethylene (PE) fiber, local recycled fine aggregate (RFA), and limestone calcined clay cement (LC3). The improvement in tensile strength and tensile ductility was attributed to the self-cementing properties of RFA as well as the pozzolanic reaction between calcined clay and cement. Carbonate aluminates were also generated owing to the reaction between calcium carbonate in limestone and the aluminates in both calcined clay and cement. The bond strength between fiber and matrix was also enhanced. At the age of 150 days, the tensile stress-strain curves of ECC containing LC3 and RFA shifted from a bilinear model to a trilinear model, and the hydrophobic PE fiber exhibited hydrophilic bonding performance when embedded in RFA-LC3-ECC matrix, which could be explained by the densified cementitious matrix as well as the refined pore structure of ECC. Moreover, the substitution of ordinary Portland cement (OPC) by LC3 resulted in energy consumption and equivalent CO2 emission reduction ratios of 13.61% and 30.34%, respectively, when the replacement ratio of LC3 is 35%. Therefore, PE fiber-reinforced RFA-LC3-ECC demonstrates excellent mechanical performance as well as considerable environmental benefits.

The Prognostic Values of Androgen Receptor in Breast Cancer.

CONTEXT.­: Whether androgen receptor (AR) expression can predict prognosis in breast cancer is under debate. OBJECTIVE.­: To analyze, retrospectively, the prognostic and treatment-predictive ability of AR status in breast cancer. DESIGN.­: A total of 5765 patients diagnosed with primary invasive breast cancer without distant metastasis in the adjuvant setting were analyzed. The propensity score-matching method was used to develop a new cohort of 3978 patients (1989 patients each) in which important prognostic factors were balanced. RESULTS.­: Positive AR expression is an independent prognostic factor for disease-free survival and overall survival. Estrogen receptor (ER)+ and progesterone receptor (PR)+ AR+ breast cancer patients had the longest survival, whereas ER-PR-AR- breast cancer patients had the shortest survival. The ER/PR/AR combinations could not predict the treatment effects for adjuvant trastuzumab but could be used for adjuvant chemotherapy and endocrine therapy selection. The worst survival was found in ER+PR-AR- patients receiving toremifene, ER+PR-AR+ patients receiving exemestane, ER+PR+AR- patients receiving anthracycline, and ER-PR-AR+ patients receiving taxanes. ER+PR-AR-, ER-PR-AR+, and ER-PR-AR- patients were associated with the worst survival among those who received radiotherapy and anthracycline plus taxanes. CONCLUSIONS.­: AR in combination with ER and PR could predict the prognosis and treatment effects of chemotherapy, endocrine therapy, and radiotherapy in the adjuvant setting.

Ultrasound-guided Versus Computed Tomography Fluoroscopy-assisted Cervical Transforaminal Steroid Injection for the Treatment of Radicular Pain in the Lower Cervical Spine: A Randomized Single-blind Controlled Noninferiority Study.

OBJECT: To estimate the contrast dispersion short-term clinical efficacy and safety of ultrasound (US)-guided transforaminal steroid injection (TFSI) compared with computed tomography (CT) guidance for the treatment of cervical radicular pain. METHOD: A total of 430 patients with cervical radicular pain from cervical herniated disk or cervical spondylosis were recruited in the randomized, single-blind, controlled, noninferiority trial. The patients were randomly assigned to receive either the US-guided or CT-guided TFSI for 1 affected cervical nerve. The dispersion pattern of contrast was monitored at the time of TFSI in both groups, using CT. Patients were assessed for pain intensity by numeric rating scale (NrS) and functional disability by Neck Disability Index (NDI) at baseline, 1 and 3 months after the intervention. Complications were also recorded. RESULTS: The satisfactory rate of contrast distribution was respectively 92.1% in US group and 95.8% in CT group. Pain reduction and functional improvement were showed in both groups during follow-up. Statistical difference was not observed in the decrease in NRS pain scores and NDI scores between 2 groups with F =1.050, P =0.306 at 1 month and F =0.103, P =0.749 at 3 months after intervention. No permanent and severe complications were observed. CONCLUSIONS: This study demonstrated that US provided a noninferior injectate spread pattern and similar improvement of radicular pain and functional status when compared with CT-guided TFSI. US may be advantageous during this procedure because it allows visualization of critical vessels and avoids radiation exposure.

Latissimus dorsi flap - the main force in breast reconstruction for breast tumor in Chinese population.

Background: The latissimus dorsi flap (LDF) is the most commonly used autologous flap for breast reconstruction (BR) in China. We conducted this study to explore the current status of BR using LDF with/without implants. Methods: This study was a single-center retrospective study that included breast tumor patients who underwent LDF breast reconstruction at Fudan University Shanghai Cancer Center (FUSCC) between 2000 and 2021. Results: We analyzed 4918 patients who underwent postmastectomy BR, including 1730 patients (35.2%) with autologous flaps. LDF was used for BR in 1093 (22.2%) patients, and an abdominal flap was used in 637 (13.0%) patients. The proportion of LDFs used in autologous BR patients decreased each year and dropped to approximately 65.0% after 2013 due to the increased use of abdominal flaps. Among these patients, 609 underwent extended LDF (ELDF) BR, 455 underwent LDF BR with implants, and 30 received a LDF as a salvage flap due to previous flap or implant failure. Patients who underwent ELDF reconstruction were older and had a higher BMI than those who received a LDF with implants. There was no significant difference in the mean postoperative hospital stay, neoadjuvant chemotherapy rates, or adjuvant radiotherapy rates between the two groups. Major complications requiring surgical intervention occurred in 25 patients (2.29%). There was no significant difference in the incidence of major complications between the two groups (P=0.542). Conclusions: LDF breast reconstruction is a well-developed and safe procedure. The duration of postoperative hospitalization nor the incidence of major complications was affected by implant use.

Tracking of Mutational Signature of SARS-CoV-2 Omicron on Distinct Continents and Little Difference was Found.

The Omicron variant is currently ravaging the world, raising serious concern globally. Monitoring genomic variations and determining their influence on biological features are critical for tracing its ongoing transmission and facilitating effective measures. Based on large-scale sequences from different continents, this study found that: (i) The genetic diversity of Omicron is much lower than that of the Delta variant. Still, eight deletions (Del 1-8) and 1 insertion, as well as 130 SNPs, were detected on the Omicron genomes, with two deletions (Del 3 and 4) and 38 SNPs commonly detected on all continents and exhibiting high-occurring frequencies. (ii) Four groups of tightly linked SNPs (linkage I-IV) were detected, among which linkage I, containing 38 SNPs, with 6 located in the RBD, increased its occurring frequency remarkably over time. (iii) The third codons of the Omicron shouldered the most mutation pressures, while the second codons presented the least flexibility. (iv) Four major mutants with amino acid substitutions in the RBD were detected, and further structural analysis suggested that the substitutions did not alter the viral receptor binding ability greatly. It was inferred that though the Omicron genome harbored great changes in antigenicity and remarkable ability to evade immunity, it was immune-pressure selected. This study tracked mutational signatures of Omicron variant and the potential biological significance of the SNPs, and the linkages await further functional verification.

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, with a high rate of morbidity. The invasion and metastasis of ESCC is the main reason for high mortality. More and more evidence suggests that metastasized cancer cells require cellular elements that contribute to ESCC tumor microenvironment (TME) formation. TME contains many immune cells and stromal components, which are critical to epithelial-mesenchymal transition, immune escape, angiogenesis/lymphangiogenesis, metastasis niche formation, and invasion/metastasis. In this review, we will focus on the mechanism of different microenvironment cellular elements in ESCC invasion and metastasis and discuss recent therapeutic attempts to restore the tumor-suppressing function of cells within the TME. It will represent the whole picture of TME in the metastasis and invasion process of ESCC.