[Renal leukocyte chemokine type 2 amyloidosis: a clinicopathological analysis of fifteen cases].

Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

The therapeutic effect of decitabine combined with HAG in acute myeloid leukemia: a retrospective case-control analysis.

OBJECTIVE: Explore the efficacy of decitabine combined with homoharringtonine + cytarabine + granulocyte colony-stimulating factor (HAG) in the treatment of acute myeloid leukemia (AML). PATIENTS AND METHODS: A retrospective analysis of clinical data of 125 patients with AML was done. Of them, 61 patients received a simple HAG treatment (HAG group), and 64 received decitabine combined with an HAG regimen (combined group). Treatment efficacy, immune function before and after the treatment, levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and incidence of adverse reactions in the two groups were compared. RESULTS: The total response rate of the combined group (84.38%) was higher than that of the HAG group (65.63%) (p < 0.05). After the treatment, levels of CD4+ and CD4+/CD8+ in both groups increased and were significantly higher in the combined group compared to the HAG group. Levels of CD8+, bFGF and VEGF decreased compared to pre-treatment levels and were significantly lower in the combined group than in the HAG group (p < 0.05). There was no significant difference in the rate of adverse reactions between the two groups (p > 0.05). CONCLUSIONS: Compared to HAG treatment alone, the combination of decitabine and HAG in the treatment of AML is safe, can significantly improve the immune function of the patients, regulate bFGF and VEGF levels, and improve overall treatment efficacy.

Clinical effectiveness of fluorouracil and cisplatin intraperitoneal perfusion combined with intravenous chemotherapy for peritoneal metastasis in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies worldwide, often accompanied by peritoneal metastasis. This work aimed to investigate the clinical efficacy of intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC. PATIENTS AND METHODS: A total of 286 patients with primary GC admitted to the hospital from March 2017 to December 2020 were recruited in the study. A 1:1 matched case-control study was conducted, with the normal control (NC) group and experimental (E) group being composed of patients who underwent the corresponding treatment for primary GC with surgery within 2 months and the same pathological tumor-node-metastasis (pTNM) stage. The NC group consisted of 143 patients receiving only intravenous chemotherapy, while the E group consisted of 143 patients receiving intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy. Baseline characteristics, clinical efficacy, complications, peritoneal recurrence and metastasis, disease-free survival (DFS), and overall survival (OS) of the patients, as well as their quality of life (QoL) after chemotherapy, were compared between groups. RESULTS: After six cycles of chemotherapy, DFS was observed in both groups (70% vs. 59%; 48% vs. 29.7%; p<0.05), so did OS (85.7% vs. 85.4%; 73.1% vs. 69.3%; p>0.05). The total effective rate of treatment in the E group (46.15%) was drastically superior to that in the NC group (27.97%), and the total recurrence and metastasis rate of the E group (23.08%) was markedly inferior to that of the NC group (83.9%) (p<0.05). The total incidence of adverse reactions in the E group (11.89%) was considerably inferior to that in the NC group (35.66%) (p<0.05). In addition, the E group had markedly superior scores for physical function (PF), emotional function (EF), role function (RF), social function (SF), and cognitive function (CF) than the NC group (p<0.05). CONCLUSIONS: Intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC had certain benefits for patients and is worth applying in clinical practice.

[Histopathological evaluation of cirrhosis reversal].

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

Characterization of pyroptosis-related genes in esophageal cancer and construction of a prognostic model.

OBJECTIVE: Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. MATERIALS AND METHODS: The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. RESULTS: A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1ß, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. CONCLUSIONS: PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.

[Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma].

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

[The efficacy and safety of nerve loop blocking in the treatment of blepharospasm in Meige syndrome].

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs. 0.0 (0.0, 1.0); Z=-12.41, P<0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P>0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs. 1.0 (0.5, 2.0); Z=-4.38, P<0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

[Advances of nanomaterials applied in ophthalmic treatment].

Nanomaterials have been used in many aspects of ophthalmic treatment. By emphasizing the ubiquitous characteristics of nanoparticles and composites, we first explained their relatively mature applications in drug delivery. Then we reviewed the research on nanomaterials in regenerative medicine and gene therapy in recent years. We also discussed the main limitations of the wider application of nanomaterials in ophthalmology: stability, biotoxicity and preclinical-clinical differences. The development of efficient and non-toxic nanomaterials, combined with appropriate transportation systems and application occasions, will provide more possibilities for the future application of nanomaterials in ophthalmic treatments.

[A preliminary exploration into the efficacy of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula].

To explore the efficacy and value of personalized surgical schemes in the repair of maxillary sinus perforation and maxillary sinus fistula based on the size of the maxillary sinus perforation and maxillary sinus fistula. A total of 28 patients with maxillary sinus perforation and maxillary sinus fistula who were admitted to the Department of Oral and Maxillofacial Surgery, Stomatology Hospital of Kunming Medical University from July 2017 to May 2020 were included to conduct a prospective case clinical study. After the inflammation in the maxillary sinus was controlled, a proper surgical repair method was selected according to the size of the perforation and fistula based on the double-layer closure technique. The diameter of the perforation and fistula was measured with the assistance of cone-beam CT. After that, the platelet rich fibrin (PRF) repair was performed on the perforation and fistula with 3 mm≤diameter<7 mm in size in 14 patients. The PRF repair and buccal flap repair were performed on the perforation and fistula with 7 mm ≤diameter<15 mm in size in 7 patients. The adjacent buccal pad repair, palatine flap repair, and buccal flap repair were performed on the perforation and fistula with 15 mm≤ diameter<25 mm in size in 4 patients. The nasolabial axial flap repair and nasolabial free flap repair were performed on the perforation and fistula with a diameter ≥25 mm in size in 3 patients. The medical follow-up was conducted in all patients in the 1st, 2nd, and 4th week after surgery, with an overall success rate reaching 96.4% (27/28) after the initial intervention. The relapse of disease occurred in one patient (4.6%) with diabetes and a smoking history in the 2nd week after surgery. Identifying a proper surgical repair method according to the size of the oral and maxillary sinus perforation and maxillary sinus fistula based on the double-layer closure technique can improve the one-time cure rate in these patients under the premise that the inflammation in the maxillary sinus can be controlled.

[Reversal of hepatic fibrosis: more evidence and more challenges].

Hepatic fibrosis is a response to various types of hepatic injury, which can lead to cirrhosis and its complications. In recent years, in patients with viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, autoimmune liver disease and others the fibrosis or even early cirrhosis can be regressed if the etiology are controlled. Liver biopsy is still the gold standard for assessing fibrosis reversal, but non-invasive methods such as transient elastography hold great promise due to the ease to use for dynamic monitoring. Mechanisms of hepatic fibrosis reversal include extracellular matrix degradation, hepatocyte regeneration, and vascular remodeling. Presently, novel agents targeting the steps of fibrosis are urgently need for achieving regression of liver fibrosis.

[Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatment].

Objective: Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients. Methods: Treatment-naïve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis. Results: Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably (P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression (OR=0.887, 95%CI: 0.802-0.981, P=0.020). Conclusions: After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

[Three cases of hemodiafiltration for the treatment of CAR-T related grade 3 - 4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors].

Objective: To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors. Methods: Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out. Results: The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months. Conclusion: HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

Development of explicit formulations of G45-based gas kinetic scheme for simulation of continuum and rarefied flows.

In this work, the explicit formulations of the Grad's distribution function for the 45 moments (G45)-based gas kinetic scheme (GKS) are presented. Similar to the G13 function-based gas kinetic scheme (G13-GKS), G45-GKS simulates flows from the continuum regime to the rarefied regime by solving the macroscopic governing equations based on the conservation laws, which are widely used in conventional Navier-Stokes solver. These macroscopic governing equations are discretized by the finite volume method, where the numerical fluxes are evaluated by the local solution to the Boltzmann equation. The initial distribution function is reconstructed by the G45 distribution function, which is a higher order truncation of the Hermite expansion of distribution function compared with the G13 distribution function. Such high order truncation of Hermite expansion helps the present solver to achieve a better accuracy than G13-GKS. Moreover, the reconstruction of distribution function makes the development of explicit formulations of numerical fluxes feasible, and the evolution of the distribution function, which is the main reason why the discrete velocity method is expensive, is avoided. Several numerical experiments are performed to examine the accuracy of G45-GKS. Results show that the accuracy of the present solver for almost all flow problems is much better than G13-GKS. Moreover, some typical rarefied effects, such as the direction of heat flux without temperature gradients and thermal creep flow, can be well captured by the present solver.

Osteogenesis and angiogenesis of a bulk metallic glass for biomedical implants.

Implantation is an essential issue in orthopedic surgery. Bulk metallic glasses (BMGs), as a kind of novel materials, attract lots of attentions in biological field owing to their comprehensive excellent properties. Here, we show that a Zr61Ti2Cu25Al12 (at. %) BMG (Zr-based BMG) displays the best cytocompatibility, pronounced positive effects on cellular migration, and tube formation from in-vitro tests as compared to those of commercial-pure titanium and poly-ether-ether-ketone. The in-vivo micro-CT and histological evaluation demonstrate the Zr-based BMG can significantly promote a bone formation. Immunofluorescence tests and digital reconstructed radiographs manifest a stimulated effect on early blood vessel formation from the Zr-based BMG. Accordingly, the intimate connection and coupling effect between angiogenesis and osteogenesis must be effective during bone regeneration after implanting Zr-based BMG. Dynamic gait analysis in rats after implanting Zr-based BMG demonstrates a tendency to decrease the pain level during recovery, simultaneously, without abnormal ionic accumulation and inflammatory reactions. Considering suitable mechanical properties, we provide a realistic candidate of the Zr61Ti2Cu25Al12 BMG for biomedical applications.

Impact of trauma centre capacity and volume on the mortality risk of incoming new admissions.

INTRODUCTION: Trauma centre capacity and surge volume may affect decisions on where to transport a critically injured patient and whether to bypass the closest facility. Our hypothesis was that overcrowding and high patient acuity would contribute to increase the mortality risk for incoming admissions. METHODS: For a 6-year period, we merged and cross-correlated our institutional trauma registry with a database on Trauma Resuscitation Unit (TRU) patient admissions, movement and discharges, with average capacity of 12 trauma bays. The outcomes of overall hospital and 24 hours mortality for new trauma admissions (NEW) were assessed by multivariate logistic regression. RESULTS: There were 42 003 (mean=7000/year) admissions having complete data sets, with 36 354 (87%) patients who were primary trauma admissions, age ≥18 and survival ≥15 min. In the logistic regression model for the entire cohort, NEW admission hospital mortality was only associated with NEW admission age and prehospital Glasgow Coma Scale (GCS) and Shock Index (SI) (all p<0.05). When TRU occupancy reached ≥16 patients, the factors associated with increased NEW admission hospital mortality were existing patients (TRU >1 hour) with SI ≥0.9, recent admissions (TRU ≤1 hour) with age ≥65, NEW admission age and prehospital GCS and SI (all p<0.05). CONCLUSION: The mortality of incoming patients is not impacted by routine trauma centre overcapacity. In conditions of severe overcrowding, the number of admitted patients with shock physiology and a recent surge of elderly/debilitated patients may influence the mortality risk of a new trauma admission.

MiR-499b-5p inhibits cervical cancer cell proliferation and induces apoptosis by targeting the Notch1 signaling pathway.

OBJECTIVE: We investigated the effect of miR-499b-5p on the tumorigenesis and development of cervical cancer by targeting the Notch1 signaling pathway to identify a new potential clinical target of cervical cancer. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the mRNA expression levels of Notch1 and miR-499b-5p in cervical cancer tissues/cell lines. Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were conducted to detect cell viability, cell migration, and cell apoptosis abilities. A Dual-Luciferase reporter assay was performed to test the binding site between miR-499b-5p and Notch1. An in vivo experiment was carried out using nude mice, and xenograft tumor models were established. RESULTS: OD450 of the SiHa and HeLa cells of the miR-499b-5p agomir group was lower than that of the miR-499b-5p agomir-NC group. More apoptotic cells and fewer invasive cells were found in the former than in the latter. MiR-499b-5p inhibited the viability and migration of cervical cancer cells and promoted their apoptosis. Further detection of the Luciferase reporter gene confirmed the binding site of miR-499b-5p to Notch1. Western blot results showed that miR-499b-5p inhibited the expression of Notch1 and activated the expression of ChK2 and p-p38MAPK. Notch1 knockdown also inhibited the viability and migration of cervical cancer cells and promoted their apoptosis. MiR-499b-5p overexpression prevented the tumorigenesis and development of cervical cancer in xenograft tumor models. CONCLUSIONS: MiR-499b-5p inhibits the proliferation of cervical cancer cells and induces their apoptosis by targeting the Notch1 signaling pathway.

[Association of hyperuricemia-induced renal damage with sirtuin 1 and endothelial nitric oxide synthase in rats].

Objective: To investigate the association of hyperuricemia-induced renal damage with sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in rats. Methods: Using the random number table method, 32 Sprague-Dawley rats were randomly divided into 4 groups: control group, model A group (the model was generated using oxonic acid potassium salt alone), model B group (hyperuricemia model was generated using oxonic acid potassium salt combined with uric acid) and resveratrol group, with 8 rats in each group. The experiment lasted 12 weeks. Serum uric acid and cystatin C levels were monitored regularly. In week 12, serum creatinine and urea nitrogen levels were measured, and the kidneys were extracted. The expression of SIRT1 and eNOS in renal tissues was measured and determined by immunohistochemistry, quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. Immunohistochemistry of alpha-smooth muscle actin combined with Masson staining was employed to evaluate the degree of renal fibrosis, and pathological changes were observed based on hematoxylin and eosin staining. Results: In week 12, the uric acid levels in both the model A and model B groups were higher than those in the control group [(316±43) µmol/L, (297±40) µmol/L vs (118±44) µmol/L, both P<0.05]. The levels of cystatin C in the model A, model B, and resveratrol groups were all higher than those in the control group [(156±20) ng/ml, (143±29) ng/ml, (128±26) ng/ml vs (62±18) ng/ml, all P<0.05]. Creatinine levels were higher in the model A and model B groups than those in the control group [(68.5±10.3) µmol/L, (64.5±13.9) µmol/L vs (43.2±10.6) µmol/L, both P<0.05]. The levels of uric acid, cystatin C and creatinine in the resveratrol group were lower than those in the model A group (all P<0.05). Immunohistochemistry, RT-qPCR, and Western blotting for renal SIRT1 and eNOS showed that the expression in the model A and model B groups was inhibited, while the expression in the resveratrol group was not significantly inhibited, compared with that in the control group. Microscopically, obvious abnormalities were not found in the renal tissue of the control group. Renal inflammatory cell aggregation and edema occurred, and interstitial fibrosis was obvious in both the model A and model B groups, while these lesions in the resveratrol group were significantly improved. Conclusions: Hyperuricemia may cause renal injury by inhibiting the expression of SIRT1 and eNOS.