Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived.

Despite recent advances in tumor diagnosis and treatment technologies, the number of cancer cases and deaths worldwide continues to increase yearly, creating an urgent need to find new methods to prevent or treat cancer. Sulforaphane (SFN), as a member of the isothiocyanates (ITCs) family, which is the hydrolysis product of glucosinolates (GLs), has been shown to have significant preventive and therapeutic cancer effects in different human cancers. Early studies have shown that SFN scavenges oxygen radicals by increasing cellular defenses against oxidative damage, mainly through the induction of phase II detoxification enzymes by nuclear factor erythroid 2-related factor 2 (Nrf2). More and more studies have shown that the anticancer mechanism of SFN also includes induction of apoptotic pathway in tumor cells, inhibition of cell cycle progression, and suppression of tumor stem cells. Therefore, the application of SFN is expected to be a necessary new approach to treating cancer. In this paper, we review the multiple molecular mechanisms of SFN in cancer prevention and treatment in recent years, which can provide a new vision for cancer treatment.

A modified lateral column lengthening for the treatment of flexible flatfoot: From clinical applications to finite element analysis.

BACKGROUND: Finite element (FE) analysis and clinical follow-up were used to evaluate the efficacy of a modified lateral column lengthening (H-LCL) for treating flexible flatfoot. METHODS: By applying inclusion and exclusion criteria, we selected patients who underwent H-LCL surgery at our institution from January 2019 to January 2023. We compared the Visual Analog Scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) scores, Pain Interference (PI), and Physical Function (PF) scores in Patient-Reported Outcomes Measurement Information System (PROMIS) between preoperative and final follow-up assessments of patients, as well as FE submodels. Furthermore, evaluate the H-LCL's biomechanical characteristics and clinical outcome before and after surgery. RESULTS: A total of 66 patients met the criteria. The average surgery time was 69.47 ± 13.22 min, and the follow-up duration was 15.18 ± 6.40 months. In the last follow-up, VAS and PI decreased compared to before surgery, while AOFAS and PF increased compared to before surgery. Meary's angle (dorsoplantar image and lateral image), calcaneal valgus angle, and talonavicular coverage angle decreased compared to before surgery, while the pitch angle increased compared to before surgery. In FE analysis, postoperative tension on the plantar fascia (PF), spring ligament (SL), and posterior tibial tendon (PTT) decreased compared to before surgery, pressure on the talonavicular joint and subtalar joints also decreased compared to before surgery, and there was no significant change in pressure on the calcaneocuboid joint. CONCLUSION: H-LCL in correcting flexible flatfoot resulted in a significant improvement of clinical outcome scores and led to good radiological correction of flatfoot deformities. It can reduce the soft tissue and interosseous pressure in maintaining the foot arch.

Improved Results From Medium and Long-Term Outcomes of Autogenous Osteoperiosteal Grafting for Large Cystic Lesions of the Talus.

PURPOSE: To investigate the medium and long-term follow-up outcomes of large cystic medial osteochondral lesions of the talus (OLTs) treated with autologous tibial osteoperiosteal grafts from the medial tibia, and to explore the risk factors influencing the treatment outcomes. METHODS: The retrospective study included 75 patients with large cystic medial OLTs who underwent autologous osteoperiosteal cylinder graft taken from the medial tibia between January 2004 and August 2018. They were assessed preoperatively and postoperatively using a visual analog scale (VAS), the Orthopedic Foot & Ankle Society Ankle-Hindfoot Scale (AOFAS) and short-form 36-item questionnaire score (SF-36). Magnetic resonance observation of cartilage repair tissue (MOCART), second-look arthroscopy, and biopsy were used to evaluate the grafting areas. RESULTS: After a follow-up period of 6.3 years, the VAS score decreased to 1.47 ± 1.32, while the AOFAS and SF-36 scores increased to 82.78 ± 11.65 and 83.26 ± 8.49, respectively, all of which showed significant improvement over preoperative scores (P < .001), and the average MOCART score was 82.6 ± 8.4 (56.0-91.6). Eight patients underwent a second-look arthroscopic examination and were rated by the International Cartilage Repair Society scale; of them, 2 patients were rated grade Ⅰ, 4 were rated grade Ⅱ, and 2 were rated grade Ⅲ. Three patients underwent grafting area biopsy during the second-look arthroscopy, and the results showed that the grafting areas were rich in chondrocytes. Large-size OLTs (≥200 mm2) and obesity (BMI ≥ 25 kg/m2) were responsible for the poor improvement of AOFAS, according to multivariate Cox regression analysis. CONCLUSIONS: Autologous osteoperiosteal grafting was an effective treatment for large cystic medial OLTs, with effective cartilage regeneration in the grafted areas in the medium and long term. However, the large-size OLTs and obesity may reduce the treatment outcomes. LEVEL OF EVIDENCE: Level IV, case series.

Double-bundle reconstruction of the anterior talofibular ligament by partial peroneal brevis tendon.

BACKGROUND: Anatomic anterior talofibular ligament (ATFL) reconstruction with autologous single-bundle tendon has been widely used in the treatment of ATFL injury. However, there are few clinical reports of using the peroneus brevis tendon (PBT) for double-bundle ATFL reconstruction. The aim of this study was to investigate the clinical effect of double-bundle ATFL reconstruction with PBT. METHODS: This was a retrospective review of all patients diagnosed with ATFL injury presenting from August 2019 to December 2021. Fifty-three patients were selected after screening based on the inclusion and exclusion criteria. The following data were compared before and after surgery: Visual Analogue Scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), the pain interference (PI) and physical function (PF) scores of the Patient-Reported Outcomes Measurement Information System (PROMIS), the diameter and width of PBT in ultrasound and muscle strength. RESULTS: All functional scores (VAS, PI/PF, AO-FAS, KAFS) and muscle strength were significantly improved at the last follow-up (P < 0.05). The diameter and width of the PBT on ultrasound postoperation were smaller than those preoperatively. CONCLUSION: Double-bundle ATFL reconstruction with the partial PBT technique is a feasible, anatomic reconstruction technique for chronic lateral instability of the ankle, which meets the anatomical characteristics of the double bundle of the ligament, and the absence of partial PBT does not affect the peroneal muscle strength. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Ultrasound-guided quadratus lumborum block for postoperative analgesia in renal surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Quadratus lumborum block (QLB) guided by ultrasound is a novel local block anesthesia technique, which can be used in various surgeries for multimodal analgesia. Its analgesic effectiveness for renal surgery is still uncertain. The aim of this meta-analysis was to assess the postoperative analgesic efficacy of QLB in adult patients undergoing renal surgery. METHODS: We systematically searched randomized controlled trials (RCTs) through the databases of Cochrane Library, Embase, and PubMed until June 21, 2021. Postoperative consumption of opioid in the first 24-h was set as the primary outcome. The risk of bias was evaluated by Cochrane methodology. RESULTS: Ten RCTs involving 577 patients were eligible for our inclusion criteria. Ultrasound-guided QLB significantly reduced postoperative consumption of opioid in the first 24 h after surgery (mean differences [MD] - 17.58, 95% confidence interval [CI] - 23.14 to - 12.02, P < 0.00001, I2 = 98%). Similarly, the results were consistent in subgroups analysis of both different types of renal surgeries and different QLB approaches. The QLB also significantly decreased postoperative static pain scores at different time points, and reduced the incidence of postoperative nausea and vomiting (PONV) (risk ratio [RR] = 0.48, 95% CI 0.33 to 0.70, P = 0.0002, I2 = 0%) and the number of rescue analgesia patients (RR = 0.34, 95% CI 0.20 to 0.58, P < 0.0001, I2 = 0%). No major complications related to QLB were reported in the included studies. CONCLUSIONS: Ultrasound-guided QLB improves postoperative analgesic efficacy and reduces PONV in adult patients undergoing renal surgery. There is currently limited evidence concerning the analgesic effects of different QLB approaches after renal surgery, and further research is required in this area. PROSPERO REGISTRATION: PROSPERO Registration CRD42021260821.

miR-149* Suppresses Liver Cancer Progression by Down-Regulating Tumor Necrosis Factor Receptor 1-Associated Death Domain Protein Expression.

Liver cancer is the third leading cause of cancer-related death worldwide. Herein, we show that miR-149* serves as a novel tumor suppressor for liver tumorigenesis. Mice with genetic deletion of miR-149* (miR-149*-/- mice), which caused loss of both miR-149 and miR-149*, were considerably more susceptible to acute liver injury and hepatic carcinogenesis induced by diethylnitrosamine than wild-type mice, accompanied by increased compensatory proliferation and up-regulated gene expression of certain inflammatory cytokines. miR-149* mimics dramatically impaired liver cancer cell proliferation and migration in vitro and blocked liver cancer progression in a xenograft model. Furthermore, miR-149* strongly suppressed NF-κB signaling and repressed tumor necrosis factor receptor type 1-associated death domain protein expression in the NF-κB signaling pathway. These results reveal that miR-149*, as a novel liver tumor suppressor, may serve as a potential therapeutic target for liver cancer treatment.

Heterotopic Ossification After Prestige-LP Cervical Disc Arthroplasty Is Related to Insufficient Sagittal Coverage of the Endplate By the Prosthesis.

BACKGROUND Heterotopic ossification (HO) is a major complication after cervical disc arthroplasty (CDR) that has attracted the attention of spine surgeons. There remains a great deal of controversy regarding the surgical risk factors. The present study investigated the correlation between insufficient sagittal coverage of the prosthesis-endplate and HO after CDR and explored strategies to prevent it. MATERIAL AND METHODS We included 73 patients who underwent Prestige-LP arthroplasty. Patients were divided into HO and non-HO groups. Related data, including radiological, clinical information, were collected. HO was graded using the McAfee classification. Analysis was performed to correlate HO to the surgical segmental range of motion (ROM) at last follow-up. To evaluate the insufficient sagittal coverage of the prosthesis-endplate and other factors for developing HO, receiver operating characteristic (ROC) curves were analyzed for insufficient sagittal coverage. RESULTS Among 73 patients, 24 patients had HO at the last follow-up (HO incidence: 32.9%). The ROM in the HO group was significantly lower (P<0.001). The insufficient sagittal coverage of the upper and lower prosthesis-endplate, the height of intervertebral space, and the preoperative and postoperative ROM were related to HO (P<0.05). Multivariate logistic regression analysis showed that only insufficient sagittal coverage of the upper prosthesis-endplate was related to HO (P=0.023), and ROC curve analysis revealed that HO was more likely to occur with insufficient sagittal coverage distance ≥2.5 mm. CONCLUSIONS HO after CDR causes a reduction in ROM, the occurrence of which is associated with insufficient sagittal coverage of the prosthesis-endplate. HO was more likely to occur with insufficient sagittal coverage distance ≥2.5 mm.

The predictive significance of bone mineral density on postoperative pain relief in knee osteoarthritis patients after total knee arthroplasty: A prediction model.

BACKGROUND: Bone mineral density (BMD) may be an important factor affecting the clinical outcomes after total knee arthroplasty (TKA). However, further information regarding BMD in postoperative pain relief is not present yet. This study aims to gain further insight into the predictive significance of BMD in postoperative pain relief in knee osteoarthritis (KOA) patients after TKA. METHODS: 156 KOA patients treated by TKA were included in this study. Visual analogue scale (VAS) was used to measure the pain intensity in patients within one year after TKA. The patients were divided into good pain relief group (the improvement of VAS ≥ 3) and poor pain relief group (the improvement of VAS < 3). BMD and other clinical characteristics were also collected. Logistic regression analysis and receiver operating characteristic curve (ROC curve) were used to evaluate the predictive significance of BMD. Subgroup analysis was used to compare the difference of postoperative pain between High BMD group and Low BMD group extra. RESULTS: 34 (21.8%) patients had poor pain relief after TKA. Logistic regression analysis indicated that age, BMD, preoperative hospital for special surgery (HSS) scores, preoperative VAS score and postoperative posterior slope angles (PSA) were the risk factors of poor pain relief (P < 0.05). Using BMD as a predictor, the optimum cut-off value of poor pain relief was T-level = -3.0 SD in the ROC curve, where sensitivity and specificity were 73.5% and 83.7%, respectively. Based on this cut-off value, obvious pain relief was observed in the High BMD group compared with Low BMD group from the 6th month after TKA in the subgroup analysis (P < 0.05). CONCLUSIONS: BMD is an effective predictor for postoperative pain relief in KOA patients after TKA, and the poor pain relief should be fully considered especially when BMD T-level ≤ -3.0 SD.

Effectiveness of Short-Segment Fixation versus Long-Segment Fixation for Degenerative Scoliosis with Cobb Angle 20°~40°: A Retrospective Observational Study.

BACKGROUND There remains a great deal of controversy regarding the selection of long-segment fixation and short-segment fixation, especially for degenerative scoliosis (DS) patients with Cobb angle 20°~40°. The purpose of this study was to investigate the effects of different fixation levels in DS patients with Cobb angle 20°~40°. MATERIAL AND METHODS We enrolled 96 DS patients, divided into a long-segment fixation group (>3 segments) and a short-segment fixation group (≤3 segments). The visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the clinical outcomes. The spinal-pelvic parameters and complications were also collected and analyzed. RESULTS The short-segment fixation group had the advantages of less blood loss, shorter operation time and shorter fluoroscopy time (P<0.05). The 2 groups achieved similar effects in leg pain (VAS) and ODI after operation (P>0.05); however, there was a better relief of low back pain in the long-segment fixation group (P<0.05). The changes of Cobb angle, sagittal vertical axis (SVA), lumbar lordosis (LL), pelvic tilt (PT) and sacral slope (SS) in the long-segment fixation group were more obvious than that in the short-segment fixation group at the final follow-up (P<0.05). The prevalence of complications in the long-segment fixation group was significantly higher than in the short-segment fixation group (P<0.01). CONCLUSIONS Short-segment fixation has less surgical trauma and fewer complications, whereas long-segment fixation has more advantages in improving spine-pelvis parameters and relieving low back pain.

Four-component acyloxy-trifluoromethylation of arylalkenes mediated by a photoredox catalyst.

A four-component intermolecular trifluoromethylation-acyloxylation of arylalkenes induced by visible light has been developed in the presence of the photoredox catalyst Ru(bpy)3(PF6)2 under mild reaction conditions. A new Umemoto's reagent was used as a trifluoromethyl radical source, and this redox neutral reaction demonstrated good functional group tolerance for aryl alkenes with high yields up to 91%. The detailed reaction process was investigated based on control, deuterium and O18-labeling experiments to support that N,N-dimethylformamide (DMF)/H2O acted as an acyloxyl source.

Powerful, Thermally Stable, One-Pot-Preparable, and Recyclable Electrophilic Trifluoromethylating Agents: 2,8-Difluoro- and 2,3,7,8-Tetrafluoro-S-(trifluoromethyl)dibenzothiophenium Salts.

Although many electrophilic trifluoromethylating agents have been reported to date, practically useful reagents have yet to be developed. S-(Trifluoromethyl)dibenzothiophenium salts, known as Umemoto's reagents, have two significant drawbacks that have hampered their practical application: (1) synthesis involving many steps and (2) the formation of large amounts of dibenzothiophene as waste after trifluoromethylation. Our idea to substitute fluorine at specific positions on the dibenzothiophenium rings has resulted in massive improvements in the synthesis, properties, reactivity, and applications of these compounds. On the basis of this idea, 2,8-difluoro- and 2,3,7,8-tetrafluoro-S-(trifluoromethyl)dibenzothiophenium triflates and other salts were developed as powerful, thermally stable, one-pot-preparable, and recyclable reagents for the trifluoromethylation of various types of nucleophilic substrates, such as carbanions, (hetero)aromatics, alkenes, alkynes, thiols, sulfinates, and phosphines. This one-pot and recycled production tremendously decreases the chemical and environmental costs of this process. Because of their higher reactivity and thermal stability, these new reagents may have wider applications than Umemoto's reagents. Therefore, these new versions of Umemoto's reagents could be widely used as the first practically useful electrophilic trifluoromethylating agents for the production of many types of trifluoromethyl-containing compounds in academic and industrial applications.

Identification, synthesis and characterization of new impurities in tenofovir.

A detailed impurity study was conducted on tenofovir, (R)-({[1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid (1), which is the key starting material of manufacturing the active pharmaceutical ingredient (API) tenofovir disoproxil fumarate (2) based on a recently reported procedure. The major impurities generated in the production of tenofovir (1) have been synthesized, characterized and confirmed. The possible formation mechanisms of these impurities were elucidated herein, which would help to understand the process. In addition, this work will also improve the quality control during manufacturing tenofovir and tenofovir disoproxil fumarate (2).

Comparison of Clinical Efficacy between Arthroscopic and Open Surgery for Ogden Type 1-2 Peroneal Tendon Dislocation.

OBJECTIVE: While the incidence of peroneal tendon dislocation (PTD) is relatively low, it is frequently underdiagnosed in clinical practice, and the misdiagnosis or improper treatment of this condition may lead to a decline in patients' quality of life. Currently, the surgical treatment options for PTD mainly include open and arthroscopic surgery. However, in order to evaluate the advantages and disadvantages of these two surgical approaches, further comparative research is needed. Therefore, the aim of this study is to investigate the early clinical outcomes of arthroscopic and open surgery in the treatment of Ogden type 1-2 PTD. METHODS: We conducted a comprehensive analysis of 46 patients diagnosed with PTD who underwent surgery at our institution between January 2017 and January 2023. The patients were divided into two groups: the open surgery group, consisting of 26 cases, and the arthroscopic surgery group, consisting of 20 cases. To compare the effectiveness of the surgical approach, we evaluated several parameters, including the integrity of the superior peroneal retinaculum on MRI images, functional scores, pain interference scores, and ankle eversion muscle strength. These assessments are conducted respectively before the surgery, 1 month after the surgery, 3 months after the surgery, and at the final follow-up for each group of patients (at least 6 months post-surgery). Demographics and intergroup comparisons of the two groups of data were analyzed by t-test or the Mann-Whitney U test. Intragroup comparisons of the two groups of data were analyzed by one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, followed by post hoc multiple comparisons. RESULTS: In the intragroup comparisons, both the arthroscopic surgery and the open surgery group demonstrated significant improvement in functional scores, pain interference scores, muscle strength, and MRI findings at the final follow-up postoperatively (p < 0.01). However, the open surgery group exhibited significant improvements in these outcomes at the final follow-up, while the arthroscopic surgery group showed significant improvement at 3 months postoperatively. In intergroup comparisons, the arthroscopic surgery group outperformed the open surgery group in functional scores, pain interference scores, and muscle strength 3 months after the surgery, with statistically significant differences (p < 0.01). CONCLUSION: Arthroscopic surgery offers advantages in early clinical outcomes, such as pain relief, function, and muscle strength improvement. However, over time, both approaches provide similar results regarding effectiveness.

Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Cu(I)-Photosensitizer-Catalyzed Olefin-α-Amino Radical Metathesis/Demethylenative Cyclization of 1,7-Enynes.

A demethylenative En-Yne radical cyclization of 1,7-enynes has been successfully developed to chemoselectively afford 3,4-dihyroquinolin-2-ones or quinolin-2-ones under the catalysis of Cu(I) photosensitizers PS3 and PS6 with different redox potentials. The preliminary mechanistic experiments revealed that the reaction underwent an unprecedented olefin-α-amino radical metathesis-type process. A reasonable mechanism was proposed to illustrate the catalyst-controlled chemoselectivity of the reaction based on preliminary mechanistic experiments and DFT calculations.

Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy.

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.

Role of G-protein coupled receptors in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of death globally, with CVDs accounting for nearly 30% of deaths worldwide each year. G-protein-coupled receptors (GPCRs) are the most prominent family of receptors on the cell surface, and play an essential regulating cellular physiology and pathology. Some GPCR antagonists, such as ß-blockers, are standard therapy for the treatment of CVDs. In addition, nearly one-third of the drugs used to treat CVDs target GPCRs. All the evidence demonstrates the crucial role of GPCRs in CVDs. Over the past decades, studies on the structure and function of GPCRs have identified many targets for the treatment of CVDs. In this review, we summarize and discuss the role of GPCRs in the function of the cardiovascular system from both vascular and heart perspectives, then analyze the complex ways in which multiple GPCRs exert regulatory functions in vascular and heart diseases. We hope to provide new ideas for the treatment of CVDs and the development of novel drugs.

Pelvic metastatic squamous cell carcinoma of unknown primary site: A case report and brief literature review.

RATIONALE: Cancer with unknown primary site is a kind of disease that is difficult to deal with clinically, accounting for 2% to 9% of all newly diagnosed cancer cases. Here, we report such a case with pelvic metastatic squamous cell carcinoma of an unknown primary site and review the relevant literature. PATIENT CONCERNS DIAGNOSES: A 43-year-old Chinese female patient was referred to our hospital and initially diagnosed as "malignant tumor of right adnexal area?, obstruction of right ureter, secondary hydronephrosis". INTERVENTIONS: Thereafter cytoreductive surgery was performed which included a total hysterectomy, left adnexectomy, partial omentum resection, pelvic lymph node dissection, and para-aortic lymph node dissection. The primary lesion could not be identified by supplementary examination and postoperative pathology. The patient was diagnosed as pelvic metastatic squamous cell carcinoma whose primary site was unknown. To prevent a recurrence, we administered adjuvant chemotherapy for the patient. OUTCOMES: The patient was followed up after treatment, complete remission has been maintained for 72 months, and no recurrence or metastasis has been found. LESSONS: Our case demonstrates that surgery combined with chemotherapy could be helpful for pelvic metastatic squamous cell carcinoma of unknown primary site.

Copper indium selenium nanomaterials for photo-amplified immunotherapy through simultaneously enhancing cytotoxic T lymphocyte recruitment and M1 polarization of macrophages.

Photoactivated immunotherapy has promising therapeutic efficacy for treating malignancies, especially metastatic tumors. In this study, an erythrocyte membrane-encapsulated copper indium selenium (RCIS) semiconductor nanomaterial was developed to eliminate primary and metastatic tumors, in which copper ions can induce chemodynamic performance, and the narrow band gap endows RCIS with the properties of near-infrared (NIR) light-activated photothermal and photodynamic amplified immunotherapy. Furthermore, RCIS can be used as a nanocarrier to form RNCIS nanoparticles (NPs) by loading NLG919, which blocks the indoleamine 2,3-dioxygenase-1. Under NIR light irradiation, RNCIS NPs release NLG919 at tumor sites via photothermal properties, thereby promoting the recruitment of cytotoxic T lymphocytes and M1 polarization of macrophages, targeting the activation and amplification of immune responses. Herein, in vitro and in vivo studies showed that RNCIS NPs effectively kill cancer cells and eliminate primary and metastatic tumors. Therefore, this study suggests that semiconductor nanomaterials with narrow bandgaps have great potential as photoimmunotherapy agents and NIR light-responsive nanocarriers for controlled release, providing a great paradigm for synergetic tumor photoimmunotherapy. STATEMENT OF SIGNIFICANCE: The Erythrocyte membrane-coated, NLG919-loaded copper indium selenium (RNCIS) semiconductor was designed for eliminating primary and metastatic tumors. RNCIS exhibits chemodynamic, photodynamic, and photothermal activated immunotherapy by inhibiting indoleamine 2,3-dioxygenase-1. This can enhance the recruitment of cytotoxic T lymphocyte and M1 polarization of macrophage, leading to higher synergetic photo-immune therapeutic efficacy.

Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1.

Circular-RNA friend leukemia virus integration 1 (circ-FLI1; hsa_circ_0000370) is a noninvasive biomarker for the diagnosis of colon carcinoma (CC). Herein, we intended to investigate its functions and competing endogenous RNA (ceRNA) mechanisms in CC cells. In terms of expression status, circ-FLI1 was abnormally upregulated in CC patients' tumors and cells, paralleled with DKC1 upregulation and miR-197-3p downregulation. Most strikingly, there was a direct target relationship between miR-197-3p and circ-FLI1 or DKC1 based on the starbase database, dual-luciferase reporter assay, and RNA immunoprecipitation. Functionally, the colony formation assay, MTS method, fluorescence-activated cell sorting method, cell cycle and apoptosis assays, and transwell assays were performed, and the results revealed that interfering circ-FLI1 and re-expressing miR-197-3p could restrict colony formation, cell viability, cell cycle progression, and migration/invasion of CC cells with apoptosis rate elevation; besides, they promoted oxaliplatin (L-OHP)-induced cell viability inhibition. Furthermore, there were counteractive effects between circ-FLI1 silencing and miR-197-3p depletion, miR-197-3p overexpression and DKC1 restoration on regulating CC cell functions and L-OHP resistance. With a xenograft tumor model, the anti-growth role of circ-FLI1 silencing was also found in vivo with or without L-OHP treatment. Collectively, we demonstrated that circ-FLI1 might confer L-OHP resistance and malignant progression of CC presumably through the circ-FLI1/miR-197-3p/DKC1 ceRNA axis.