Emerging role of necroptosis, pyroptosis, and ferroptosis in breast cancer: New dawn for overcoming therapy resistance.

Breast cancer (BC) is one of the primary causes of death in women worldwide. The challenges associated with adverse outcomes have increased significantly, and the identification of novel therapeutic targets has become increasingly urgent. Regulated cell death (RCD) refers to a type of cell death that can be regulated by several different biomacromolecules, which is distinctive from accidental cell death (ACD). In recent years, apoptosis, a representative RCD pathway, has gained significance as a target for BC medications. However, tumor cells exhibit avoidance of apoptosis and result in treatment resistance, which emphasizes further studies devoted to alternative cell death processes, namely necroptosis, pyroptosis, and ferroptosis. Here, in this review, we focus on summarizing the crucial signaling pathways of these RCD in BC. We further discuss the molecular mechanism and potentiality in clinical application of several prospective drugs, nanoparticles, and other small compounds targeting different RCD subroutines of BC. We also discuss the benefits of modulating RCD processes on drug resistance and the advantages of combining RCD modulators with conventional treatments in BC. This review will deepen our understanding of the relationship between RCD and BC, and shed new light on future directions to attack cancer vulnerabilities with RCD modulators for therapeutic purposes.

Endoscopic thyroidectomy via chest-collarbone approach versus conventional open thyroidectomy: a retrospective comparative study.

OBJECTIVE(S): Endoscopic thyroidectomy, such as axillary, areola and transoral approaches, offer the advantage of a good cosmetic outcome, but it requires a wider dissection field compared to open thyroidectomy. Recently, chest-collarbone approach thyroidectomy has been widely developed in China because of its shorter anatomical route compared to other endoscopic approaches. This study retrospectively evaluated endoscopic thyroidectomy via chest-collarbone approach in patients with thyroid nodules to determine its feasibility. METHODS: A total of 46 patients with thyroid disease who underwent endoscopic thyroidectomy between January 2022 and December 2022 were enrolled in the study and randomly matched to patients with thyroid disease who underwent open thyroidectomy at the same time based on nodule size and pathology. Postoperative bleeding, hoarseness situation, hospital stay, postoperative drainage volume, laryngeal nerve palsy, hypoparathyroidism and wound infection were assessed in both groups. RESULTS: Forty-four patients underwent endoscopic thyroidectomy successfully and two patients changed to open thyroidectomy. The amount of postoperative drainage for the endoscopic thyroidectomy group was 102.78 ±â€¯28.04 mL, and which was 71.91 ±â€¯19.20 for open thyroidectomy group (p < 0.001). The postoperative hospital stay for the endoscopic thyroidectomy group was 8.78 ±â€¯2.57 days, and which was 7.22 ±â€¯1.13 for open thyroidectomy group (p < 0.001). There was no significant difference in postoperative bleeding, hoarseness situation, and wound infection between the two groups. Laryngeal nerve palsy, supraclavicular nerve injury and hypoparathyroidism were not observed in any patient during this study. CONCLUSION: Chest-collarbone endoscopic thyroid surgery is acceptable. This treatment improves in a good cosmetic outcome in patients with thyroid disease. To assess patients with preoperative nodule size and nature of the case is the impact of the success rate, which is particularly important.

tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming.

tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5'tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.

Expression and clinical significance of undifferentiated embryonic cell transcription factor 1 in breast cancer.

Background: At present, due to the heterogeneity of breast cancer, common tumor markers have certain limitations in clinical prognostic evaluation. This suggests an unmet need for markers to predict clinical outcomes and potentially guide targeted therapies. The present study sought to explore the expression level and clinical significance of undifferentiated embryonic cell transcription factor 1 (UTF1) in breast cancer. Methods: Immunohistochemistry (IHC) was used to detect the expression of UTF1 in 221 breast cancer samples. The clinical significance of UTF1 protein expression in breast cancer tissues was evaluated by combining clinicopathological parameters and UTF1 expression profile. We performed 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays to evaluate the effect of UTF1 on Bcap37 cell proliferation. Wound healing assay and transwell migration assay were used to evaluate the changes of cell invasion and migration ability, respectively. All experiments were performed with 3 biological replicates. Genomic differences after UTF1 overexpression were evaluated by RNA sequencing technology and the possible functions and regulatory mechanisms were elucidated. Results: The findings showed that UTF1 expression level was significantly correlated with tumor size (P=0.004), but not with patient age, tumor histological stage, lymph node metastasis, as well as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki67 expression levels. Kaplan-Meier survival analysis and Cox proportional hazard model indicated that UTF1 expression was significantly associated with overall survival (OS) time of breast cancer patients. The median survival time of patients with high expression level of UTF1 was shorter compared with that of patients with low UTF1 expression level. The results of cell experiments showed that UTF1 overexpression could significantly promote the growth, proliferation, migration, and invasion of breast cancer cells. The RNA sequencing results showed that UTF1 was not only closely related to apoptosis genes, but also closely related to the nuclear factor (NF)-kappa B pathway. Conclusions: The findings of the current study indicate that UTF1 is involved in occurrence and tumor progression and is significantly associated with prognosis of breast cancer patients.

Insight into the physiological and pathological roles of USP44, a potential tumor target (Review).

Ubiquitin-specific peptidase 44 (USP44) is a member of the ubiquitin-specific proteases (USPs) family and its functions in various biological processes have been gradually elucidated in recent years. USP44 targets multiple downstream factors and regulates multiple mechanisms through its deubiquitination activity. Ubiquitination is, in essence, a process in which a single ubiquitin molecule or a multiubiquitin chain binds to a substrate protein to form an isopeptide bond. Deubiquitination is the catalyzing of the isopeptide bonds between ubiquitin and substrate proteins through deubiquitylating enzymes. These two processes serve an important role in the regulation of the expression, conformation, localization and function of substrate proteins by regulating their binding to ubiquitin. Based on existing research, this paper summarized the current state of knowledge about USP44. The physiological roles of USP44 in various cellular events and its pathophysiological roles in different cancer types are evaluated and the therapeutic potential of USP44 for cancer treatment is evaluated.

[Treatment of the recurrent lumbar disc herniation:a comparison between endoscopic surgery and open surgery].

OBJECTIVE: To compare the clinical effect,advantages and disadvantages of endoscopic surgery and open surgery in treating the recurrent lumbar disc herniation. METHODS: From August 2008 to December 2010,the data of 35 patients with recurrent lumbar disc herniation were retrospectively analyzed. The patients were divided into endoscopic surgery group and open surgery group according to operative methods. Fourteen patients in endoscopic surgery group were treated with transforaminal lumbar interbody fusion by micro-endoscopic discectomy (MED) and the other 21 patients in open surgery the group were treated with posterior lumbar interbody fusion by open surgery. All patients were fixed by vertebral pedicle screw. The operation time,volume of bleeding and drainage after operation,analgesic dosage and time in bed after operation were observed. Visual Analogue Scale(VAS),Japanese Orthopedic Association(JOA)and Chinese Oswestry Disability Index(CODI) were used to evaluate the clinical effects before and after operation. RESULTS: There was no significant difference in operation time between two groups(P>0.05). Volume of bleeding and drainage after operation,analgesic dosage and time in bed after operation,VAS score in endoscopic surgery group was less than that of open surgery group (P<0.01). All patients were followed up for 1 year. There was no significant difference in JOA between two groups (P>0.05). CODI in endoscopic surgery group was better than that of open surgery group (P<0.01). CONCLUSION: Both operative methods can obtain good clinical effects,but the transforaminal lumbar interbody fusion operation by micro-endoscopic discectomy (MED) has advantage of less traumatic and less pain,better functional recovery,it is a first choice in treating the recurrent lumbar disc herniation.

[Postmenopausal osteoporosis of liver and kidney deficiency type treated with acupoint catgut embedding by stages].

OBJECTIVE: To explore the better treatment of postmenopausal osteoporosis of liver and kidney deficiency type. METHODS: One hundred and five cases were randomly divided into an observation group, a control group A and a control group B equally. In control group A, Calcichew D3 tablets were taken with oral administration; in control group B, Calcichew D3 tablets and Xianling Gubao capsule were taken with oral administration. In observation group, Calcichew D3 tablets and acupoint catgut embedding were applied; Shenshu (BL 23), Ganshu (BL 18), Jiaji (EX-B 2) and Weizhong (BL 40) etc. were selected at acute stage; Shenshu (BL 23) and Ganshu (BL 18) etc. were selected at remission stage, once every half a month and 6 months treatment in all. The Visual Analogue Scale (VAS), bone mineral density(BMD), estradiol (E2) and clinical effects were compared among groups. RESULTS: After 3 and 6 months treatment, the scores of VAS were reduced among groups (all P < 0.01); the reduction in observation group and control group B was superior to that in control group A (all P < 0.001), and it was more obvious in observation group than that in control group B (both P < 0.001). After 6 months treatment, lumbar BMD and the serum level of Ez improved obviously in observation group and control group B (all P < 0.01). The comparison among groups after treatment showed that the BMD in observation group and control group B was superior o o that in control group A (P < 0.01, P < 0.05); the serum level of E2 in observation group was superior to that in control group B and control group A (both P < 0.001), and it in control group B was superior to that in control group A. The total effective rate was 91.4% (32/35) in observation group, superior to that in control group A (57.1%, 20/35); and the total effective rate was 82. 9% (29/35) in control group B, superior to that in control group A. CONCLUSION: Calcichew D3 tablets and acupoint catgut embedding therapy can relieve the pain caused by postmenopausal osteoporosis of liver and kidney deficiency, improve the bone mineral density and serum level of estradiol; in brief, it is the better method.

[Controlled clinical trials on the treatment and prevention of shoulder and back fasciitis using horizontal bar exercises].

OBJECTIVE: To explore an exercise method for the prevention and treatment of the patients with shoulder and back fasciitis. METHODS: From 2006.8 to 2008.3, 120 patients with shoulder and back fasciitis were randomly divided into control group (n = 60, including 21 females and 39 males, the average age was (47.0 +/- 12.0) years, and the average course of disease was (14.1 +/- 12.0) months) and treatment group (n = 60,including 19 females and 41 males, the average age was (43.7 +/- 9.9) years, and the average course of disease was (16.4 +/- 13.4) months). The patients in the control group received massage therapy and the ones in the treatment group were treated with massage therapy and horizontal bar exercise. After 3 weeks treatment, the curative effects of the patients in two groups were observed. All the patients were followed up for 6 to 26 months, the recurrence were observed. RESULTS: After 3 weeks treatment, the scores of pain, sense of heaviness, strip sign, tenderness, shoulder and back function of the patients in two groups had significant differences compared with those before treatment (all P < 0.01). After treatment, the scores of pain, sense of heaviness, strip sign, tenderness, shoulder and back function of the patients in the treatment group were lower than those in the control group (P < 0.05). After 6 to 26 months following-up, the rate of recurrence in the treatment group was lower than that in the control group (P < 0.01). CONCLUSION: Horizontal bar exercise is a simple, no expense and effective method in the prevention and treatment of shoulder and back fasciitis, which can improve the effect of the treatment and reduce the rate of recurrence.

[Case-control study on embracing knee and rolling lumbar training for preventing and treating degenerative osteoarthritis of lumbar spine].

OBJECTIVE: To study therapeutic effects of embracing knee and rolling lumbar (EKRL) training on the pain and the function of lumbar of patients with degenerative osteoarthritis of lumbar spine. METHODS: From 2006.8 to 2008.1, 150 patients with degenerative osteoarthritis of lumbar spine were randomly divided into the control group, EKRL training group and the combined group. In the control group (n=50), there were 16 females and 34 males, the average age was (58.8 +/- 10.2) years and the average course of diseases was (16.3 +/- 14.9) months. In the EKRL training group (n=50), there were 13 females and 37 males, the average age was (60.1 +/- 8.2) years and the average course of disease was (17.1 +/- 15.3) months. In the combined group (n=50), there were 15 females and 35 males, the average ages was (59.9 +/- 11.4) years and the average course of diseases was (19.8 +/- 17.2) months. The patients in three groups were treated with Meloxicam tablets, EKRL training and two above methods combination respectively. After 3 weeks treatment, the curative effect, the visual analogous scores and the ODI indexes were observed. All the patients were followed up and the duration ranged from 6 to 24 months; the changes of average ODI indexes were observed monthly. RESULTS: After 3 weeks treatment, the therapeutic effects in three groups had obvious difference after Ridit analyses: there were significant differences between the combined group and other two groups (P<0.01), but no obvious differences existed in other two groups. Compared with before treatment, the visual analogue scale scores and the ODI indexes in three groups reduced significantly (P<0.01). After treatment, the visual analogue scale scores and the ODI indexes of the combined group had significant differences compared with those of other two groups (P<0.01), but the ODI indexes of other two groups had no obvious differences. After 6 to 24 months following-up, the monthly changes of average ODI indexes of EKRL training and combined groups had obvious differences compared with that of the control group (P<0.01). CONCLUSION: EKRL training is a simple, no expense and effective methods for preventing and treating degenerative osteoarthritis of lumbar spine.

[Analysis of intermediate and long term clinical effects on discectomy with diskoscope].

OBJECTIVE: To estimate intermediate and long term clinical effects of lumbar intervertebral disc herniation on discectomy with diskoscope. METHODS: A hundred and nine patients with lumbar intervertebral disc herniation were retrospectively analyzed. The patietnts were operated with diskoscope. There were 61 males and 48 females. The age was from 25 to 68 years old with an average of 37.7 years. The affected region of patients were L(3,4) (5 cases), L(4,5) (42 cases), L5S1 (49 cases), L(4.5) and L5S1 (13 cases). Among them, 88 cases with single side and one segment, 13 cases with homolateral and two segments, 8 cases with hibateral and one segment were operated. The curative effects were followed up and estimated by recording satisfaction degrees at 1 year and 5.2 years(average) after operation. Moreover,intervertebral space height and the spinal stability of the patients were compared by imaging data before and after operation. RESULTS: At 1 year and 5.2 years (average) after operation,the scores by JOA standard were improved from 6.40 +/- 1.68 to 13.40 +/- 1.42, 13.15 +/- 1.35 (P < 0.01) respectively;the scores by VAS standard were reduced from 7.10 +/- 1.55 to 1.90 +/- 0.84, 2.10 +/- 0.58 (P < 0.01) respectively; the excellent and good rate was 91.7% (100/109) and 89.9% (98/109) respectively; the satisfaction degree of the patients was 95.4% and 94.5% respectively. The average time before working was 1 month. The imaging data of 45 patients were complete in the study, no lumbar instability sign were found. The loss rates of intervertebral space height were 57.8% (26/45), 93.3% (42/45) respectively at 1 year and 5.2 years (average) after operation. CONCLUSION: Discectomy with diskoscope has a good intermediate and long term clinical effects, it is a reliable method in the treatment of lumbar intervertebral disc herniation. It doesn't uncertainly cause instability of intervertebral space and root compression, though it can't avoid the loss of intervertebral space height.