Objective: To explore the diagnosis, treatment and prognosis of primary prostatic signet ring cell carcinoma (SRCC), so as to provide reference for the clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with primary prostatic SRCC treated in Nanjing Drum Tower Hospital during Nov.2020 and Sep.2024.The clinical manifestations, imaging features, treatment methods, histological characteristics and prognosis were summarized. Results: The average age of the patients was (72.00±4.28) years.Varying degrees of dysuria occurred in 4 patients. All patients underwent multi-parametric magnetic resonance imaging (mpMRI) examination before surgery, and the results indicated typical prostate cancer.Preoperative biopsies showed high-grade (Gleason 8-10) prostate acinar adenocarcinoma.Postoperative pathological diagnoses were mixed types of prostate acinar adenocarcinoma and SRCC, and no metastasis was found in the pelvic lymph nodes.All patients were followed up for 1 to 46 months after surgery and are currently alive.Robot-assisted laparoscopic radical prostatectomy only was performed in 3 cases; apalutamide and leuprolide/triptorelin was administered after surgery in 2 cases; bicalutamide + goserelin was administered after surgery in 1 case, who developed bladder metastasis of prostate cancer 24 months later, and the serum prostate-specific antigen (PSA) concentration decreased to a safe level (<0.2 ng/mL) after the use of darolutamide with radiotherapy.No recurrence or metastasis was found in the remaining patients. Conclusion: Primary prostatic SRCC is a rare and highly aggressive malignant tumor of the prostate.The diagnosis depends on pathological examinations due to lack of specific imaging features and clinical manifestations.The prognosis is poor, and there is currently no standardized treatment.The combined use of surgery, hormonotherapy and radiotherapy can help improve the survival rate of patients.

Objective To investigate the effect of N6-methyladenosine (m⁶A) reading protein human antigen R (HuR) on the migration, invasion and glycolysis of colorectal cancer cells and its relationship with 6-phosphofructokinase 1 (PFK1). Methods The tissue samples of 33 patients who were first diagnosed as colorectal cancer in Zhengzhou Central Hospital Affiliated to Zhengzhou University from April to December 2022 were collected. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of HuR and PFK1 mRNA in colorectal cancer tissues and adjacent tissues. The expression of HuR mRNA in normal intestinal epithelial cells NCM460 and colorectal cancer cells HCT8, SW480, SW620, HCT116, LoVo, RKO and COLO205 was detected. Small interfering RNA (siRNA) was used to construct a HuR knockdown colorectal cancer cell model. The effects of HuR on the migration and invasion of colorectal cancer cells were detected by cell scratch assay and Transwell assay. The expression of PFK1 mRNA and protein was detected by qRT-PCR and Western blot. Glucose intake and pyruvate production were detected by glucose content kit and pyruvate content kit, respectively. The relationship between HuR and PFK1 was analyzed by bioinformatics analysis, and the effect of HuR on the stability of PFK1 mRNA was evaluated by actinomycin D assay. Results In colorectal cancer tissues, HuR and PFK1 were highly expressed at mRNA level; HuR was highly expressed at mRNA level in colorectal cancer cell lines. Down-regulation of HuR significantly inhibited the migration and invasion of colorectal cancer cells, as well as glucose consumption and pyruvate production. Knockdown of HuR could reduce the stability of PFK1 mRNA and its expression at mRNA and protein levels. There were m⁶A modification sites on PFK1. Conclusion The m⁶A reading protein HuR may regulate the migration, invasion and glycolysis of colorectal cancer cells by recognizing the m⁶A site on PFK1 and reducing the stability of PFK1 mRNA.

Objective To investigate the expression and mechanism of long non-coding RNA (lncRNA) GHRLOS2 in colorectal cancer tissues and cells. Methods Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of GHRLOS2 and microRNA-33b-5p (miR-33b-5p) in colorectal cancer tissues or cells. Overexpressing of GHRLOS2 in HCT116 and SW480 colorectal cancer cell lines were constructed, and the effects of overexpression of GHRLOS2 on the migration and invasion abilities in HCT116 and SW480 cell lines were detected by wound healing assay and Transwell assay. Glucose content in cells of overexpressing GHRLOS2 and control cells was detected using a glucose detection kit. Western blot was used to detect the expression level of PCK1 protein in cells. The targeted binding relationship between miR-33b-5p and PCK1 was predicted based on bioinformatics methods. Results The qRT-PCR results showed that the expression level of GHRLOS2 in colorectal cancer tissue samples was lower than that in adjacent non-cancerous tissues, and was lower in colorectal cancer cells than that in normal colon epithelial cells (P < 0.05). The expression of GHRLOS2 was correlated with grade classification, staging, and lymph node metastasis (P < 0.05). The expression level of miR-33b-5p in colorectal cancer tissues was higher than that in corresponding adjacent non-cancerous tissues (P < 0.001). The results of wound healing assay, Transwell assay, and glucose content detection showed that overexpression of GHRLOS2 significantly inhibited the invasion, migration, and glucose metabolism of colorectal cancer cells. Overexpression of GHRLOS2 inhibited the expression level of miR-33b-5p; GHRLOS2 functioned as a molecular sponge for miR-33b-5p, and PCK1 was a target of miR-33b-5p; overexpression of GHRLOS2 competitively bound to miR-33b-5p, thereby promoting increased expression of PCK1. Conclusion The expression of GHRLOS2 is downregulated in colorectal cancer tissues and cells, and it may regulate the invasion, migration, and glucose metabolism of colorectal cancer cells through the miR-33b-5p/PCK1 pathway, making it a potential biological target for targeted therapy of colorectal cancer.

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC. METHODS: We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients. RESULTS: The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low. CONCLUSIONS Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.
Humans ; Squamous Cell Carcinoma of Head and Neck ; Proto-Oncogene Proteins c-myc/metabolism* ; Laryngeal Neoplasms/diagnosis* ; Carcinoma, Squamous Cell/genetics* ; Lymphatic Metastasis ; Prognosis ; Head and Neck Neoplasms ; Biomarkers, Tumor/metabolism* ; RNA-Binding Proteins/genetics*

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC 50 ) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDL-RAD3 knockdown decreased the IC 50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.

Objective:Severe trauma events are emergent, with low incidence and unpredictable. Current guideline does not provide precise recommendations on how the trauma centers should arrange the number of beds in trauma intensive care units while making rational use of medical resources. We analyzed the trauma intensive care unit bed requirement in the branch campus of our hospital to propose a reasonable assessment.Methods:Patients with severe trauma sent to the Intensive Care Unit of Peking University People's Hospital from January 2022 to June 2022 were collected. The daily number of patients received intensive care was counted. The bed requirement of the intensive care unit covering 99% of clinical needs was calculated based on the probability distribution function.Results:From January 2022 to June 2022, 103 patients with severe trauma [74 males and 29 females, aged (51.47±16.06) years, ranging 16 to 87 years] were included in the study. Among the 103 patients, 57 were injured in traffic accidents, 26 fell from a high altitude, 12 fell, 4 were hit by heavy objects, and 4 were stabbed. TISS ranged from 16 to 50. The range of the daily bed requirement in the intensive care unit was 0–10, which was consistent with the Poisson distribution. According to the probability distribution function, nine trauma intensive care beds could meet 99.19% of clinical needs.Conclusions:In severe traumatic events, patients need to be transferred to intensive care unit as soon as possible. For our branch campus, nine trauma intensive care beds can cover more than 99% of clinical needs. It follows that, in accordance with the basic requirements of trauma center construction, hospitals with trauma centers need at least 9 beds in intensive care units. However, traumatic events cannot be predicted; thus, the bed requirement needs to be regularly evaluated.

Objective:To investigate the clinical effects of expanded frontal flap and flip scar flap in repairing partial nasal defect.Methods:A retrospective observational study was conducted. From January 2012 to January 2022, 26 patients with partial nasal defects who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 19 males and 7 females, aged 5 to 61 years. The surgery was performed in 4 stages. In the first stage, a rectangular skin and soft tissue expander (hereinafter referred to as expander) with suitable rated capacity was planted in frontal region and expanded by injecting water regularly. In the second stage, flip scar flap was grafted to reconstruct nasal inner lining, whose area was about 10% larger than the area of defect. The expanded frontal flap with pedicle was transferred to repair the nasal defect, whose pedicle was supraorbital vessel or supratrochlear vessel on the contralateral side of the defect, and the area of expanded flap was 20% larger than the nasal defect area after resection and flipping of scar flap. The donor site of expanded flap was sutured directly. After 3 weeks of flap transferring, the flap was delayed in the third stage. After 1 week of delaying operation, the pedicle of flap was cut off in the fourth stage. The number, rated capacity, injection volume, and expansion time of embedded expanders were recorded. The occurrences of complications including infection, hematoma, ulceration of expanded flap after the first stage operation, and blood supply disorder or necrosis of flap after operation in the second and fourth stages were observed. All the patients were followed up for 1 year at least, and the color of flap, scar of frontal donor site, symmetry of bilateral eyebrows, and the nasal appearance and ventilated function of external nasal tract were observed.Results:A total of 26 expanders were embedded in 26 patients. The rated capacity of expanders ranged from 100 to 300 mL. The injection volume was 1.0 to 1.5 times of the rated capacity of expanders. The expansion time ranged from 2.5 to 4.0 months, with an average time of 3 months. There were no complications occurred after each operation. The follow-up showed that the color of flap was similar to the normal nasal skin, the scar of frontal region was not obvious, the bilateral eyebrows were basically symmetrical, the nose had excellent appearance, ventilation function of external nasal tract was not affected, while some of the patients had downward rotation or unapparent tip-defining point of nose.Conclusions:Using the flip scar flap to reconstruct the nasal inner lining and pre-expanded frontal flap to reconstruct the nasal skin, without free cartilage transplantation to repair the partial nasal defects can achieve satisfied nasal appearance post operation, without abnormal external nasal ventilation function.

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment