Oncoplastic breast-conserving surgery improves cosmetic outcomes without increasing recurrence risk compared to modified radical mastectomy in early breast cancer patients: development and validation of a recurrence risk prediction model.

In the quest for effective treatment of early-stage breast cancer, this study aimed to compare the clinical efficacy of modified radical mastectomy (MRM) and oncoplastic breast-conserving surgery (OBCS). Breast cancer remains a major health concern globally, where early detection and effective treatment strategies are crucial for improving the outcomes of patients. MRM and OBCS are two primary treatment modalities for breast cancer, each with its distinct benefits and challenges. Through a retrospective analysis, we found that although the patients in the OBCS group experienced a longer operation time, they had significantly less intraoperative bleeding, postoperative drainage, and hospitalization time compared to the MRM group. Furthermore, patients in the OBCS group demonstrated higher subjective satisfaction and quality of life scores, along with better objective outcomes. In terms of postoperative complications and recurrence rates, no significant difference was identified between the two groups. However, our multivariate Cox regression analysis identified lymph node metastasis and molecular type as independent prognostic factors for disease-free survival (DFS). Subsequently, we constructed a risk model based on these variables, which was proven to be effective in predicting recurrence, with an area under the risk score curve for recurrence prediction being 0.852. The group with a lower risk score demonstrated a significantly higher DFS rate. Our study suggests that compared with MRM, OBCS can significantly reduce surgical incision, improve patient satisfaction, and does not increase the risk of complications or recurrence. Our risk model, developed using Cox regression, also demonstrated high clinical value in predicting breast cancer recurrence, thereby aiding in personalized patient management and treatment planning.

Evaluation of indocyanine green combined with methylene blue staining in sentinel lymph node biopsy of breast cancer.

Background: Methylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer. Methods: One hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups. Results: A total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P<0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P<0.05). Conclusions: ICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

[Short-segment pedicle screw fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis].

OBJECTIVE: To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis. METHODS: Twenty-four patients with Kümmell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed. RESULTS: All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (P<0.05). Two patients had complications, including asymptomaticcement leakage in 1 patient and superficial wound infection in 1 patient. CONCLUSION: Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kümmell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kümmell disease with kyphosis.

The role of the programmed cell death protein-1/programmed death-ligand 1 pathway, regulatory T cells and T helper 17 cells in tumor immunity: a narrative review.

Tumor immunotherapy, especially that involving programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive checkpoint inhibitors, has become an important part of tumor treatment strategy in the past decade. Blocking PD-1/PD-L1 signaling pathway can reduce the inhibitory effect of PD-1 pathway on T cells, promote the anti-tumor activity of activated T cells, and prolong the remission period of tumor. While PD-1/PD-L1 immunotherapy is effective in the treatment of solid malignant tumors, it also has shortcomings, due to the complexity of the tumor microenvironment (TME). Regulatory T cells (Tregs) and T helper 17 (Th17) cells play an important role in the TME and are closely related to the occurrence and development of tumors. Tregs can inhibit the anti-tumor immune effect, while Th17 cells play a dual role in tumor immunity, which not only promotes tumorigenesis but also promotes anti-tumor immunity. In the occurrence and development of tumor, PD-1/PD-L1 pathway, Tregs and Th17 cells are interrelated. However, the complicated relationship between the PD-1/PD-L1 pathway, Tregs, and Th17 cells has not been fully clarified. Here, we summarize the immunoregulation mechanisms and discuss the crosstalk between the PD-1/PD-L1 pathway, Tregs, and Th17 cells, with the aim of providing novel insights for future cancer treatment.

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin.

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15µgkg-1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

Painful Schmorl's nodes treated by discography and discoblock.

PURPOSE: To determine the efficacy of discography and discoblock in the treatment of low back pain (LBP) associated with painful Schmorl's nodes (SNs). METHODS: Between January 2010 and February 2015, 46 patients were studied who had LBP suspected to be secondary to SNs. There were 34 men and 12 women, and mean age was 54.2 years (range 42-68 years). All patients underwent provocation discography, and discoblock was given to positive patients (confirmed to have painful SNs). Visual analogue scores (VAS) and the Oswestry Disability Index (ODI) were evaluated at 4 h and 1, 3, 6, and 12 months post-operatively. MRI was also used to evaluate the SNs at 12 months. RESULTS: Discography was performed on a total of 60 discs without infection or other complications. Positive findings were found in 71.7% discs; 20.0% were negative, and 8.3% were indeterminate. Among the positive patients who underwent discoblock, 89.2% reported an improvement in their LBP, and none reported worsening symptoms. VAS and ODI scores decreased significantly after discoblock, and there were no significant differences between 4 h and 1, 3, 6, and 12 months post-operatively. In patients with painful SNs, the vertebral body bone marrow surrounding the SN was characterized by low T1 and high T2 signals on MRI. At 12 months, the node demonstrated either high T1 and T2 signals or low T1 and T2 signals. The SNs tended to remain stable in size over time. CONCLUSIONS: Painful SNs refractory to medical or physical therapy should be an indication for treatment with discography and discoblock.

Role of amygdala kisspeptin in pubertal timing in female rats.

To investigate the mechanism by which maternal obesity disrupts reproductive function in offspring, we examined Kiss1 expression in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei, and posterodorsal medial amygdala (MePD) of pre-pubertal and young adult offspring. Sprague-Dawley rats were fed either a standard or energy-dense diet for six weeks prior to mating and throughout pregnancy and lactation. Male and female offspring were weaned onto normal diet on postnatal day (pnd) 21. Brains were collected on pnd 30 or 100 for qRT-PCR to determine Kiss1 mRNA levels. Maternal obesity increased Kiss1 mRNA expression in the MePD of pre-pubertal male and female offspring, whereas Kiss1 expression was not affected in the ARC or AVPV at this age. Maternal obesity reduced Kiss1 expression in all three brain regions of 3 month old female offspring, but only in MePD of males. The role of MePD kisspeptin on puberty, estrous cyclicity and preovulatory LH surges was assessed directly in a separate group of post-weanling and young adult female rats exposed to a normal diet throughout their life course. Bilateral intra-MePD cannulae connected to osmotic mini-pumps for delivery of kisspeptin receptor antagonist (Peptide 234 for 14 days) were chronically implanted on pnd 21 or 100. Antagonism of MePD kisspeptin delayed puberty onset, disrupted estrous cyclicity and reduced the incidence of LH surges. These data show that the MePD plays a key role in pubertal timing and ovulation and that maternal obesity may act via amygdala kisspeptin signaling to influence reproductive function in the offspring.

Derivation and Validation of a Clinical Prediction Scale for Isolated Distal Deep Venous Thrombosis in Patients after Acute Ischemic Stroke.

BACKGROUND: Isolated distal deep venous thrombosis (IDDVT) is a common complication after ischemic stroke. However, there is a paucity of evidence regarding the clinical features and risk factors of IDDVT in patients with acute ischemic stroke. This study aimed to establish and validate a clinical prediction scale of IDDVT at an early stage of ischemic stroke development. METHODS: We retrospectively studied consecutive patients with stroke admitted to our neurology department between January and December 2016. Selected clinical variables were assessed by multivariable logistic regression to determine the independent risk factors for IDDVT. A prediction scale was developed and verified by the receiver operating characteristic curve. RESULTS: A total of 671 patients with ischemic stroke were included in the study, with 450 patients allocated into the derivation group and 221 patients into the validation group. A substantial proportion (22.1%) of patients developed IDDVT. A 16-point prediction scale (female gender = 2, older age [≥60 years] = 3, atrial fibrillation = 2, acute infection = 2, active cancer = 5, and higher [≥2.6 mmol/L] level of low-density lipoprotein = 2) derived from a multivariable logistic regression model was highly predictive of 10-day risk of IDDVT in both the validation group (c statistic = .70, 95% confidence interval [CI], .63-0.78, P < .0001) and the derivation group (c statistic = .68, 95% CI, .63-0.74, P < .0001). CONCLUSIONS: This prediction scale may help to identify patients with ischemic stroke who are at a higher risk of developing IDDVT.

Propionibacterium acnes Incubation in the Discs Can Result in Time-Dependent Modic Changes: A Long-Term Rabbit Model.

STUDY DESIGN: A case-control study of animal model of Modic changes (MCs) on rabbits. OBJECTIVE: To evaluate the feasibility of inducing of MCs by injection of Propionibacterium acne (P. acnes) into the lumbar intervertebral discs of rabbits. SUMMARY OF BACKGROUND DATA: MCs have been widely observed, and assume to be closely associated with low back pain and P. acnes, but there are few animal models showing the progression of MCs. METHODS: Ten rabbits were used for the study. The L3-4 and L4-5 discs of all rabbits were injected with 100 µL P. acnes (1.6 × 10 CFU/mL) as P. acnes group, L2-3 disc were injected with 100 µL normal saline as vehicle, and L5-6 disc was untreated (blank). MCs were investigated by magnetic resonance imaging before operation and at 2 weeks, 1, 3, 4.5, 6, and 9 months postoperatively. Following sacrifice, histological analysis, blood test and micro-computed tomography were performed. Cytokine expression in nucleus and endplate tissues was quantified using real-time polymerase chain reaction. RESULTS: From 3 months postoperatively, the P. acnes group showed significantly decreased T1-weighted signal intensity, whereas the T2-weighted signal was significantly higher at 3 and 4.5 months, and then decreased remarkably at 6 and 9 months. Eleven of 20 inferior endplates were identified as type I MCs at 4.5 months, and 9 of 20 were identified as type II MCs at 9 months. Real-time polymerase chain reaction showed that expression of interleukin-1ß, tumor necrosis factor α, interferon-γ, matrix metalloproteinase-9, and thrombospondin motifs-5 in the nucleus pulposus, and interleukin-1ß, tumor necrosis factor α, and thrombospondin motifs-5 in the endplates, were significantly upregulated after injection of P. acnes. Histological slices of discs injected with P. acnes showed disc degeneration, endplate abnormalities, and inflammatory response, with micro-computed tomography confirming bone resorption. CONCLUSION: P. acnes infection of the disc can induce degeneration of the disc and an inflammatory response in the endplate region, presenting as MCs type I and II time dependently. LEVEL OF EVIDENCE: N/A.

The Influence of Direct Inoculation of Propionibacterium acnes on Modic Changes in the Spine: Evidence from a Rabbit Model.

BACKGROUND: Modic changes (inflammatory-like changes visible on magnetic resonance imaging [MRI] scans of a vertebral end plate) are common and are associated with low back pain, but their origin is unclear. To our knowledge, there have been no previous in vivo animal models of Modic changes. We hypothesized that Modic changes may be related to Propionibacterium acnes. METHODS: Ten New Zealand White rabbits were injected percutaneously with 1 mL of P. acnes (1.6 × 10 colony forming units/mL) into the subchondral bone superior to the L4-L5 and L5-L6 discs; 10 other control rabbits received sham injections at L4-L5 and 1 mL of normal saline solution (vehicle) at L5-L6. The subchondral bone superior to L3-L4 discs was untreated (blank). Development of Modic changes was investigated with MRI studies before the operation and at 2 weeks and 1, 2, 3, and 6 months postoperatively. Following sacrifice of the rabbits, histological analysis and microcomputed tomography (micro-CT) were performed, and blood samples were analyzed. Cytokine expression in end-plate tissues was quantified using real-time polymerase chain reaction (PCR). RESULTS: The group that received P. acnes showed significantly increased T1-weighted signal intensity at 6 months (mean and standard deviation, 3.43 ± 0.41 [range, 2.42 to 4.44] compared with 2.43 ± 0.66 [range, 1.98 to 2.87] before the injection) and higher T2-weighted signal intensity at 6 months. Positive culture results were obtained from 9 of 20 samples injected with P. acnes. Specimens with positive cultures had a higher prevalence of Modic changes (4 of 9 samples positive for P. acnes compared with 3 of 11 samples negative for P. acnes). Real-time PCR showed significantly increased expression of tumor necrosis factor-α, interleukin-1ß, and interferon-γ following injection of P. acnes, but no changes were seen on histological analysis, micro-CT, or blood analysis. CONCLUSIONS: P. acnes can survive within the end-plate region and can initiate mild inflammatory-like responses from host cells, leading to signal intensity changes in MRI scans, which potentially resemble Modic changes. CLINICAL RELEVANCE: Disc degeneration and low back pain are associated with Modic changes. Our results indicate that Modic changes can be associated with P. acnes in the conjunction area of the disc and subchondral bone. These results may be useful for understanding the underlying mechanisms of Modic changes and related pain.

Biodegradable and biocompatible high elastic chitosan scaffold is cell-friendly both in vitro and in vivo.

Biodegradable and biocompatible macromolecule chitosan has been favored for a variety of clinical applications. We reported herein the fabrication of a novel chitosan scaffold with high elasticity. This scaffold can be easily compressed and thus enable the insertion of such scaffold into surgical lesions during minimal invasive surgeries. In addition, this novel scaffold can restore its shape when released. We evidenced that this high elastic scaffold has better biocompatibility than traditional chitosan scaffold. Therefore, this new chitosan material might lead to the manufacture of a variety of novel biodegradable biomedical materials and devices.

Kisspeptin in the medial amygdala and sexual behavior in male rats.

The medial amygdala (MeA) is crucial for sexual behavior; kisspeptin (Kiss1) also plays a role in sexual function. Kisspeptin receptor (Kiss1r) knockout mice display no sexual behavior. Recently Kiss1 and Kiss1r have been discovered in the posterodorsal subnucleus of the medial amygdala (MePD). We hypothesised that Kiss1 in the MePD may have an influence on male sexual behavior. To test this we bilaterally cannulated the MePD and infused kisspeptin-10 in male rats. This caused the rats to have multiple erections, an effect specific to Kiss1 receptor activation, because Kiss1r antagonism blocked the erectile response. When Kiss1 was infused into the lateral cerebroventricle, there were no observed erections. We also measured the plasma levels of LH when Kiss1 is infused into the MePD or lateral cerebroventricle; Kiss1 increased plasma LH to comparable levels when infused into both sites. We conclude that Kiss1 has a role in male sexual behavior, which is specific to the MePD.

Mini-open Anterior Lumbar Interbody Fusion for Recurrent Lumbar Disc Herniation Following Posterior Instrumentation.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study is to evaluate, clinically and radiographically, the efficacy of mini-open retroperitoneal anterior lumbar discectomy followed by anterior lumbar interbody fusion (ALIF) for recurrent lumbar disc herniation following primary posterior instrumentation. SUMMARY OF BACKGROUND DATA: Recurrent disc herniation following previous disc surgery occurs in 5 to 15% of cases. This is often treated by further surgical intervention where posterior approach is generally preferred. However, posterior surgery may be problematic if the initial surgery involved posterior instrumentation. An anterior approach may be indicated in these patients, and recent findings suggest that a "mini-open" procedure may have some benefits when compared with traditional open techniques and their associated morbidities. METHODS: A total of 35 recurrent lumbar disc herniation patients (10 male, 25 female) following primary posterior instrumentation with an average age of 52.8 years (range: 34-70 yrs) who underwent the mini-open ALIF procedures between August 2001 and February 2012 were evaluated retrospectively. The ALIF was performed at the levels L4-L5 (n = 14), L5-S1 (n = 15), or both L4-L5 and L5-S1 (n = 6). Visual Analog pain Scale (VAS) and Oswestry Disability Index (ODI) together with radiological results were assessed. RESULTS: The mean operating time, intraoperative estimated blood loss, and hospital stay were 115 minutes, 70 mL, and 6 days, respectively. No blood transfusion was needed. Transient complication was recorded in two patients. Postoperative follow-up was a minimum 24.3 months. VAS score and ODI percentage decreased significantly from 7.9 ±â€Š0.8 and 78.8% ±â€Š12.4% pre-operatively to 1.4 ±â€Š0.6 and 21.7 ±â€Š4.2% at final follow-up, respectively. There was no neurological worsening and radicular pain improved significantly compared with pre-operation in all the patients. Computed tomographic reconstruction 12 and 24 months after surgery showed bony fusion, normal position, and morphology of the fusion cage in all patients. CONCLUSION: Mini-open retroperitoneal ALIF is an effective treatment for patients with recurrent lumbar disc herniation following primary posterior instrumentation. LEVEL OF EVIDENCE: 4.

Kisspeptin signaling in the amygdala modulates reproductive hormone secretion.

Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to hypothalamic centers involved in gonadotropin secretion. We therefore hypothesized that kisspeptin has effects on neuronal activation and reproductive pathways beyond the hypothalamus and particularly within the amygdala. To test this, we mapped brain neuronal activity (using manganese-enhanced MRI) associated with peripheral kisspeptin administration in rodents. We also investigated functional relevance by measuring the gonadotropin response to direct intra-medial amygdala (MeA) administration of kisspeptin and kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked decrease in signal intensity in the amygdala compared to vehicle alone. This was associated with an increase in luteinizing hormone (LH) secretion. In addition, intra-MeA administration of kisspeptin resulted in increased LH secretion, while blocking endogenous kisspeptin signaling within the amygdala by administering intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse frequency. We provide evidence for the first time that neuronal activity within the amygdala is decreased by peripheral kisspeptin administration and that kisspeptin signaling within the amygdala contributes to the modulation of gonadotropin release and pulsatility. Our data suggest that kisspeptin is a 'master regulator' of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion.

Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer.