Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Kidney stones is the most common urinary system disease, among which calcium oxalate stones are the most common. The pharmacological treatment of calcium oxalate stones currently in use is associated with low compliance and a high incidence of adverse reactions. In recent years, plant extracts have demonstrated considerable potential in inhibiting renal calcium oxalate stones. This article introduces the role of plant extracts, including polysaccharides, polyphenols, alkaloids, flavonoids and organic acids, in the inhibition of calcium oxalate stones. It also provides a theoretical basis for the clinical prevention and treatment of calcium oxalate stones.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective:The extranodal extension（ENE） is widely found in head and neck squamous cell carcinoma（HNSCC）, which displays the aggressiveness of the tumor and increasing the risk of local recurrence and distant metastasis, so the ENE often has been used as an important indicator of prognosis and treatment. Although the pathologic and radiologic tests are currently the main diagnostic techniques for ENE, there is still a lack of uniform standards. The article reviews the prognostic value, pathologic and radiologic diagnosis of ENE in HNSCC over the recent years.
Humans ; Head and Neck Neoplasms/pathology* ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/diagnosis* ; Carcinoma, Squamous Cell/diagnosis* ; Extranodal Extension ; Neoplasm Recurrence, Local ; Lymphatic Metastasis

Although percutaneous nephrolithotomy (PCNL) is widely applied, there are also some serious complications, and the regional application in is uneven. In order to standardize the development and promotion of PCNL, the International Alliance of Urolithiasis(IAU) has developed the first professional guideline on PCNL. IAU-PCNL guideline covers all aspects of the whole PCNL procedure, including preoperative preparation, operation process, observation and prevention of complications, etc. The present paper would like to interpret the key contents of the IAU-PCNL guideline.

Although great progress has been made in the treatment of renal calcium oxalate stones, the incidence and recurrence rate are still high. Functional nanomaterials refer to nanomaterials with specific functions after physical or chemical action.Their role in the treatment of renal calcium oxalate stones has been widely recognized in recent years. Functional nano-materials can be divided into nano-enzymes, nano-drugs and nano-carriers according to their functions. Nano-enzymes and nano-drugs can prevent and treat calcium oxalate kidney calculi by using their physical and chemical properties or drugs. Nano-carriers can treat kidney stones by delivery of the drugs. The purpose of this paper is to describe the application of functional nanomaterials in the prevention and treatment of renal calcium oxalate stones, to summarize the mechanism of inhibiting the formation of renal calcium oxalate stones and the direction of clinical treatment in the future.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To evaluate the clinical significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma. Methods:Patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were eligible. All received 2 cycles of pembrolizumab combined with docetaxel and platinum neoadjuvant induction therapy. After two cycles, the efficacy was evaluated, followed by radical chemoradiotherapy or surgery and adjuvant chemoradiotherapy according to the efficacy. The primary endpoints were objective response rate（ORR） ，larynx-preservation（LP） rate at 3 months post-treatment and the adverse reactions during neoadjuvant therapy. Results:From December 2021 to December 2022, 10 patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were enrolled. After 2 cycles of the neoadjuvant therapy, 2 patients achieved complete response（CR）, 7 patients achieved partial response（PR）, 1 patient was stable disease（SD）, objective response rate（ORR） was 90%, and disease control rate（DCR） was 100%. 5 patients received radical chemoradiotherapy, 5 patients received surgery and adjuvant chemoradiotherapy, four of them received partial laryngectomy and partial hypopharyngeal resection surgery, and one of them received total laryngectomy and partial hypopharyngeal resection surgery. All patients were able to withstand adverse reactions of neoadjuvant therapy and successfully completed the whole treatment of HPSCC without grade 3-4 treatment-related adverse reactions. There was no recurrence or metastasis during 3-18 months of follow-up. 1 patient died of severe pneumonia 3 months after the completion of radical chemoradiotherapy. At 3 months after treatment, the larynx-preservation rate was 80%. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy has good short-term efficacy and the adverse reactions were tolerable. It can improve the larynx-preservation rate of patients with locally advanced HPSCC, thus improving the prognosis and quality of life of patients.
Humans ; Squamous Cell Carcinoma of Head and Neck/etiology* ; Neoadjuvant Therapy ; Quality of Life ; Cisplatin ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Larynx ; Head and Neck Neoplasms ; Immunotherapy

Objective:To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. Methods:A retrospective analysis was conducted on the clinical data of 91 patients with T3 glottic laryngeal cancer. Results:Among the 91 patients, 58 cases （63.7%） had anterior invasion and 33 cases （36.3%） had posterior invasion. The posterior invasion was significantly correlated with invasions of the dorsal plate of cricoid cartilage （P<0.001）, arytenoid cartilage （P= 0.001）, and subglottic region（P = 0.001）. There was no statistical difference in survival outcomes between the total laryngectomy group and the partial laryngectomy group. But in the partial laryngectomy group, the 5-year disease-free survival（DFS） of patients with anterior invasive tumors was better than that of patients with posterior invasion tumors （HR: 4.681, 95%CI 1.337-16.393, P=0.016）, and subglottic invasion was associated with worse loco-regional recurrence-free survival（LRRFS）（HR: 3.931, 95%CI 1.054-14.658, P=0.041）. At the same time, we found that involvement of the dorsal plate of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in partial laryngectomy patients （HR:11.67, 95%CI 1.89-71.98,P=0.008）. Conclusion:Compared with total laryngectomy, selected partial laryngectomy can also achieve favorable oncological outcomes. Posterior invasion and subglottic extension are independent prognostic factors for recurrence of partial laryngectomy in T3 glottic laryngeal cancer, and the involvement of the dorsal plate of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of laryngeal cancer should be further subdivided in order to select a more individualized treatment plan.
Humans ; Prognosis ; Laryngeal Neoplasms/pathology* ; Retrospective Studies ; Laryngostenosis/surgery* ; Carcinoma, Squamous Cell/pathology* ; Postoperative Complications/surgery* ; Laryngectomy