Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.

Collecting duct carcinoma with retroperitoneal mass as initial presentation: a rare case report.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare renal tumor, originating from the distal collecting duct. CDC rarely presents as a primary tumor outside the renal system. CASE PRESENTATION: In this study, we report a rare case of collecting duct carcinoma, with an initial presentation of retroperitoneal lymph node metastasis, and no identifiable primary renal tumor on CT, at the time of diagnosis. The patient was a 64-year-old man presenting with lower back pain. Preoperative CT showed a round, soft tissue mass, measuring 6.7 × 4.4 × 3.3 cm, in the left retroperitoneum with no exact occupying lesion in the left kidney. Clinically, ectopic pheochromocytoma was considered to be a differential diagnosis, and tumor resection was performed. Postoperative pathological results demonstrated that the mass was a fused lymph node, and the tumor cells were destroying the structure. The final diagnosis was lymph node metastatic collecting duct carcinoma, by histology and immunohistochemistry. No further treatment was performed as no space occupying lesion was found in the kidney. Three months later, CT was reexamined, and a mass of 3.6 cm in diameter, was found in the lower left kidney, along with multiple soft tissue masses, in the left renal hilum. Considering recurrence or metastasis, the patient was recommended to undergo surgical treatment, but the patient refused. Four months later, CT was re-examined. The tumor had rapidly progressed but the patient refused treatment again. As per the author's press release (eleven months after the first discovery), the patient is still alive. CONCLUSION: CDC is a rare malignant renal carcinoma, with a high chance of rapid progress, regional lymph nodes involvement and metastasis. It presents diagnostic challenges to clinicians and pathologists, particularly, in the absence of radiographically detectable intrarenal lesions. Definite diagnosis is based on pathological examination combined with immunohistochemical staining.

Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage.

Sanguisorba officinalis L., a traditional Chinese medicine, is frequently used to treat burns and scalds. But even so, it is unknown whether S. officinalis L. can accelerate diabetic wounds (DW) healing. Here, to bridge the gap, we employed in vivo and in vitro evaluations to assess the positive effect of S. officinalis L. ethanol extract (ESO) on DW. Results demonstrated that ESO dramatically improved the DW healing rate. With ESO treatment, the inappropriately elevated levels of IL6, IL1ß and TNFα in DW were reduced, while the expression of IL10 was increased, indicating that the abnormal inflammation in DW was also under control. Moreover, the abnormally elevated expression of CD86 was significantly inhibited and the expression of CD206 was significantly up-regulated following treatment with ESO. The global level of NF-κB protein was not affected by ESO treatment, but it suppressed the expression of phosphorylated NF-κB and prevented its nuclear entry. In addition, in RAW264.7 cells activated with lipopolysaccharide (LPS), the expression of NLRP3, Caspase1 and IL1ß were significantly diminished following ESO treatment. In conclusion, ESO was proved to be a promising treatment for DW healing due to its potential to accelerate the healing process by suppressing the inflammatory response. This was achieved by increasing the ratio of M2 to M1 polarization through blocking the NF-κB/NLRP3 signaling pathway.

Risk and treatment of symptomatic epidural hematoma after anterior cervical spine surgery: A retrospective clinical study.

Symptomatic epidural hematoma (SEH) after anterior cervical spine surgery is very rare, but it has disastrous consequences for the patients. Timely diagnosis and evaluation can effectively reduce the sequelae of neurological deficit in SEH. The purpose of this study was to retrospectively analyze a subset of clinical data of SEH after anterior cervical spine surgery, and to investigate the risk factors and treatment experience of this serious complication.Neurological deterioration after anterior cervical spine surgery was detected in six patients. Epidural hematoma was confirmed by emergency cervical magnetic resonance imaging (MRI). The patients included five males and one female, with an average age of 56.7 ±â€Š13.1 years (range 42-76 years). Three patients had a history of drinking and/or smoking. All of the patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) preoperatively, but without anticoagulant drugs or pre-spinal surgery. The coagulation function was normal in all patients. Except for one patient, who had lower blood pressure (BP) during the operation and higher BP after the operation, the other patients had a normal level of BP during the pre-, intra-, and post-operation periods. The average time was 9.9 ±â€Š6.7 hours (range, 2-19 hours) from the postoperative period to the initial neurological deficit and 6.3 ±â€Š6.0 hours (range, 1.8-16.7 hours) from the initial deterioration to evacuation. Five patients underwent emergency evacuation, and one patient underwent conservative treatment. Four patients who underwent evacuation and one patient who received conservative treatment achieved neurological function recovery with an American Spinal Injury Association (ASIA) grade 2.4 ±â€Š0.9 (range, 2-4 score) score at the last follow-up. One patient with confirmed arterial epidural hemorrhage during the evaluation showed no neurological function recovery at the last follow-up.Wide exposure of the epidural space and BP level during the perioperative period play an important role in the formation of SEH after anterior cervical spine surgery. Arterial epidural hematoma has serious consequences; therefore, early diagnosis and evaluation play an important role in the recovery from paralysis.

Is It Necessary to Perform the Second Surgery Stage of Anterior Debridement in the Treatment of Spinal Tuberculosis?

OBJECTIVE: In this retrospective comparative study, the efficacy and clinical outcomes of long posterior instrumentation, with or without laminectomy, were evaluated and the necessity of the second stage of anterior debridement in the treatment of spinal tuberculosis (TB) was discussed. METHODS: This retrospective study included 41 patients who were diagnosed with spinal TB between January 2010 and June 2016. A total of 18 patients had received long posterior instrumentation, with or without laminectomy (group A), whereas the other 23 patients had posterior instrumentation plus anterior debridement and autogenous bone grafting (group B). The surgical information, clinical effectiveness, laboratory tests, and imaging results were compared between the 2 groups. RESULTS: One patient in group B died. Sinus drainage and incomplete bone fusion were discovered 1 year postoperatively. TB symptoms were significantly improved after surgery compared with those before surgery (P < 0.05), and there was no significant difference in the treatment efficacy between the 2 groups at the final follow-ups (P > 0.05). Compared with those of group B, the surgical time, bed-rest time, and hospitalization time of group A were all significantly shorter (P < 0.05), whereas the times before abscesses disappeared, bone graft fusion, and erythrocyte sedimentation rate returning to normal were all significantly longer (P < 0.05). CONCLUSIONS: Single-stage long posterior instrumentation, with or without laminectomy, is a safe, effective, and feasible method for the treatment of spinal TB. The second stage of anterior debridement surgery may not be necessary for every spinal TB treatment.

Breast mucoepidermoid carcinoma: a case report and review of literature.

Breast mucoepidermoid carcinoma (MEC) is clinically rare, with an estimated incidence of 0.2-0.3% of all primary breast tumors. To date, only 41 cases have been reported in the literature. Herein, we present a case of breast MEC diagnosed at our hospital. The clinicopathologic features were preliminarily discussed by reviewing the literature. A 42-year-old Chinese woman presented with a lump in her right breast that was detected approximately three months prior. A microscopic examination showed that the breast MEC was composed of different proportions of mucinous cells, intermediate cells, and epidermoid cells. Most mucinous cells were positive for cytokeratin 7, while the epidermoid and intermediate cells were positive for p63 and cytokeratin 5/6. All tumor cells were negative for other myoepithelial markers, such as calponin. Tumor cells did not express estrogen, progesterone, or the HER-2/neu protein. After the patient underwent mastectomy, she was diagnosed with a low-grade mucoepidermoid carcinoma based on the clinical, histologic, and immuno-phenotypic characteristics. Our findings provide further insight into the pathologic mechanism of MEC, as correct diagnosis is essential for patient management.

[Application of ultrasonic osteotome in the posterior lumbar interbody fusion surgery by unilateral fenestration and bilateral decompression in the treatment of degenerative lumbar spinal stenosis].

OBJECTIVE: To compare the effectiveness of posterior lumbar interbody fusion (PLIF) by unilateral fenestration and bilateral decompression with ultrasounic osteotome and traditional tool total laminectomy decompression PLIF in the treatment of degenerative lumbar spinal stenosis. METHODS: The clinical data of 48 patients with single-stage degenerative lumbar spinal stenosis between January 2017 and June 2017 were retrospectively analyzed. Among them, 27 patients were treated with unilateral fenestration and bilateral decompression PLIF with ultrasonic osteotome (group A), and 21 patients were treated with total laminectomy and decompression PLIF with traditional tools (group B). There was no significant difference in gender, age, stenosis segment, degree of spinal canal stenosis, and disease duration between the two groups ( P>0.05), which was comparable. The time of laminectomy decompression, intraoperative blood loss, postoperative drainage volume, and the occurrence of operation-related complications were recorded and compared between the two groups. Bridwell bone graft fusion standard was applied to evaluate bone graft fusion at last follow-up. Visual analogue scale (VAS) score was used to evaluate the patients' lumbar and back pain at 3 days, 3 months, and 6 months after operation. Oswestry disability index (ODI) score was used to evaluate the patients' lumbar and back function improvement before operation and at 6 months after operation. RESULTS: The time of laminectomy decompression in group A was significantly longer than that in group B, and the intraoperative blood loss and postoperative drainage volume were significantly less than those in group B ( P<0.05). There was no nerve root injury, dural tear, cerebrospinal fluid leakage, and hematoma formation during and after operation in the two groups. All patients were followed up after operation, the follow-up time in group A was 6-18 months (mean, 10.5 months) and in group B was 6-20 months (mean, 9.3 months). There was no complication such as internal fixation fracture, loosening and nail pulling occurred during the follow-up period of the two groups. There was no significant difference in VAS scores between the two groups at 3 days after operation ( t=1.448, P=0.154); the VAS score of group A was significantly lower than that of group B at 3 and 6 months after operation ( P<0.05). The ODI scores of the two groups were significantly improved at 6 months after operation ( P<0.05), and there was no significant difference in ODI scores between the two groups before operation and at 6 months after operation ( P>0.05). At last follow-up, according to Bridwell criteria, there was no significant difference in bone graft fusion between the two groups ( Z=-0.065, P=0.949); the fusion rates of groups A and B were 96.3% (26/27) and 95.2% (20/21) respectively, with no significant difference ( χ 2=0.001, P=0.979 ). CONCLUSION: The treatment of lumbar spinal stenosis with unilateral fenestration and bilateral decompression PLIF with ultrasonic osteotome can achieve similar effectiveness as traditional tool total laminectomy and decompression PLIF, reduce intraoperative blood loss and postoperative drainage, and reduce lumbar back pain during short-term follow-up. It is a safe and effective operation method.

Desmoid Tumor Presenting as a Typical Cervical Dumbbell Tumor: Case Report and Review of the Literature.

BACKGROUND: Dumbbell-shaped tumor is a type of inner and outer cervical spinal canal tumor, and most of these are neurogenic. Desmoid tumors are rare, and, to the best of our knowledge, no case of desmoid tumors involving intervertebral foramen formed dumbbell-shaped tumors in the cervical spine have been reported before in English literature. Here we report a case of a desmoid tumor occurring in the cervical spine that is presented as a typical dumbbell-shaped tumor. CASE DESCRIPTION: A 47-year-old woman was admitted to our department with a mass in the left side of her neck. The tumor was initially thought to be a neurogenic cervical dumbbell tumor based on physical and radiologic examination. Postoperative hematoxylin-eosin staining and immunohistochemical staining verified the diagnosis of a cervical dumbbell desmoid tumor, which, to our knowledge, had never been reported before. We report our experience and reviewed literature regarding desmoid tumor to share our experience and explore proper treatment options of such lesions. CONCLUSIONS: Desmoid tumors in the head and neck may present as cervical dumbbell-shaped tumors. Before the treatment plan was made, thorough examinations, including surgical pathology, were necessary.

Differences Between the Intestinal Lumen Microbiota of Aberrant Crypt Foci (ACF)-Bearing and Non-bearing Rats.

BACKGROUND: Multiple factors including host-microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process. AIM: The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer. METHODS: To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing. RESULTS: The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P < 0.01). At the genus level, no significant difference was observed in the most predominant genus, Lactobacillus. Instead, Bacteroides and Prevotella were significantly less abundant (P < 0.01), while Akkermansia was significantly more abundant (P < 0.05) in ACF-bearing group at the 13th week. CONCLUSION: Imbalance of the intestinal microbiota existed between ACF-bearing and non-bearing rats, which could be used as biomarker to predict the genesis of precancerous lesions in the gut.

[Efficacy comparison between one-stage combined posterior and anterior approaches and simple posterior approach for lower lumbar tuberculosis].

Objective: To compare the clinical efficacy between one-stage combined posterior and anterior approaches (PA-approach) and simple posterior approach (P-approach) for lower lumbar tuberculosis so as to provide some clinical reference for different surgical procedures of lower lumbar tuberculosis. Methods: A retrospective analysis was made on the clinical data of 48 patients with lower lumbar tuberculosis treated between January 2010 and November 2014. Of them, 28 patients underwent debridement, bone graft, and instrumentation by PA-approach (PA-approach group), and 20 patients underwent debridement, interbody fusion, and instrumentation by P-approach (P-approach group). There was no significant difference in gender, age, course of the disease, and destructive segment between 2 groups ( P>0.05). The operation time, blood loss, bed rest time, visual analogue scale (VAS) and complication were recorded and compared between 2 groups; American Spinal Injury Association (ASIA) grade was used to evaluate the nerve function, Bridwell classification and CT fusion criteria to assess bone fusion, erythrocyte sedimentation rate (ESR) to evaluate the tuberculosis control, and Oswestry disability index (ODI) to estimate lumbar function. Results: The operation time, blood loss, and the bed rest time of the P-approach group were significantly less than those of the PA-approach group ( P<0.05). Iliac vessels rupture was observed in 1 case of the PA-approach group and sinus tract formed in 2 cases of the P-approach group. The patients were followed up 13-35 months (mean, 15.7 months) in the PA-approach group and 15-37 months (mean, 16.3 months) in the P-approach group. At last follow-up, common toxic symptom of tuberculosis disappeared and the ASIA scale was improved to grade E. The VAS score and ESR at 1 year after operation and last follow-up, and ODI at last follow-up were significantly improved when compared with preoperative ones in 2 groups ( P<0.05), but there was no significant difference between the 2 groups ( P>0.05). During follow-up, no internal fixation broken, loosening, or pulling was found. Bridwell bone fusion rates were 89.29% (25/28) and 80.00% (16/20) respectively, and CT fusion rates were 96.43% (27/28) and 90.00% (18/20) respectively, showing no significant difference between the 2 groups ( P>0.05). Conclusion: Both one-stage PA-approach and simple P-approach could obtain good clinical efficacy. The PA-approach should be selected for patients with anterior-vertebral destroy, presacral or psoas major muscles abscess, and multiple vertebral body destroy, while P-approach should be selected for patient who could gain a good debridement evaluated by imaging before operation, especially for patients with middle-vertebral body destroy, block the iliac blood vessels and old patients.