[Progressive necrotizing xanthogranuloma in both eyes: a case report].

A 55-year-old male patient presenting with 6 months of bilateral difficulty in eye opening was referred to the ophthalmology department. Upon examination, multiple yellowish tumor-like plaques and nodules were observed on the eyelids and chest of the patient, accompanied by keratitis and iridocyclitis. Histopathological examination of the skin lesions on the chest revealed dermal xanthomatous granulomas with progressive necrosis. Bone marrow biopsy showed mantle cell lymphoma. Based on the medical history, the diagnosis of progressive necrotizing xanthogranuloma with mantle cell lymphoma was confirmed. After 6 months of treatment with bendamustine combined with rituximab, there was partial alleviation of ocular symptoms in the patient.

[Microglia differential genes and their functions in paraquat-induced Parkinson's disease-like in mice's brains based on single-cell RNA sequencing].

Objective: To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals. Methods: In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 µmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) . Results: Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 µmol/L PQ-treated BV2 cells compared with the 0 µmol/L, and the differences were statistically significant (P<0.05) . Conclusion: Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375- 3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3'-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

Factors affecting neurodevelopmental outcome following surgical necrotising enterocolitis: a systematic review.

Surgically treated necrotising enterocolitis (sNEC) is associated with significantly worse neurodevelopmental outcomes than that seen in premature infants without NEC. We aim to review the association between factors involved in the surgical treatment of NEC and subsequent neurodevelopmental outcomes to identify potential areas for improvement. The PubMed and Embase databases were interrogated for articles reporting neurodevelopmental outcomes in babies treated surgically for NEC using key terms including: "Infant", "Necrotising enterocolitis", "Surgical", "Neurodevelopmental" and "Outcomes". The search strategy yielded 1170 articles and after applying inclusion and exclusion criteria 22 studies remained and formed the review. A diverse range of neurodevelopmental outcomes were reported. Extreme prematurity and lower birth weight were associated with worse neurodevelopmental outcomes. The use of peritoneal drains and enterostomies were associated with worse outcomes. Modifications to surgical strategies in NEC may improve neurodevelopmental outcomes but the effect of confounding factors remains unclear. Further large scale studies are required to define the optimum strategies for treating NEC surgically and to develop a core outcome set for research into NEC.

[Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases].

Objective: To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. Methods: This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results: After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group (P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups(P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions: PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.

[Staged and segmented two hybrid surgeries for total repair of Debakey type â aortic dissection: a series of 10 cases].

Objective: To examine the efficacy and experience of staged and segmented two hybrid surgeries for total repair of Debakey type Ⅰ aortic dissection (TIAD). Methods: This study was a retrospective case series. The clinic data of 10 patients with acute TIAD who were admitted to the Department of Cardiac Surgery, Second Hospital of Lanzhou University or the First People's Hospital of Lanzhou, between January 2016 and August 2022, were retrospectively studied. Ten patients underwent hybrid surgeries in two hospitalizations (stages), including 7 males and 3 females with an age of (60±7) years (range: 49 to 71 years). In stage 1, the first type Ⅱ hybrid arch repair was performed to treat the ascending, total arch, and descending thoracic aorta for acute TIAD without circulatory arrest. In stage 2, the second hybrid surgery including infrarenal abdominal aorta replacement, visceral arteries bypass and endovascular thoracoabdominal aortic repair was performed to treat residual thoracoabdominal aortic dissection after the first hybrid operation (segmented). Basic data, preoperative concomitant diseases, high-risk factors, surgical approaches and postoperative complications of all important organs, as well as CT imaging were analyzed. Results: There was no death in the 20 hybrid surgical procedures. In stage 1 type Ⅱ hybrid surgery, 4 cases underwent reconstruction of the aortic sinutubular junction, while Bentall and David surgery was performed for 3 cases, respectively. A patient received coronary artery bypass grafting. Then all patients were sequentially treated with arch debranching and thoracic aortic endovascular repair. Postoperative complications included renal insufficiency (4/10), hemofiltration (1/10), hypoxemia (4/10), neurologic event (1/10) and type Ⅱ endoleak (1/10). Complete false lumen thrombosis occurred in 9/10 of the patients. All complications recovered successfully at discharge and the average hospital stay was (21±4) days (range: 16 to 28 days) in the first hospitalization. At stage 2, the second hybrid surgery was successfully performed in all patients. No paraplegia, hepatic or renal insufficiency, or endoleak occurred. However, branch graft embolism of the left renal artery was found in one patient 3 days after laparotomy, as well as of superior mesenteric artery in another. Superior mesenteric artery occlusion was successfully treated by endovascular recanalization. Complete false lumen thrombosis occurred in all patients. Although all patients had different degrees of intestinal dysfunction, they were gradually relieved at discharge, and the average hospital stay was (19±2)days (range:16 to 21 days) in the second hospitalization. During follow-up, CT angiography showed aortic remodeling in all patients. Conclusion: Staged and segmented two hybrid surgeries are safe and feasible for total repair of Debakey type Ⅰ aortic dissection and are associated with acceptable early and midterm outcomes.

[Adjuvant therapy strategies for breast cancer based on the efficacy of neoadjuvant therapy].

With the advent of the precision cancer therapy era, neoadjuvant therapy has become the standard therapy for certain types of breast cancer. Neoadjuvant therapy is a fundamental treatment plan implemented at the time of disease diagnosis, and its efficacy can guide the formulation of subsequent adjuvant therapy strategies. Building on the efficacy of neoadjuvant therapy and medication regimens, in conjunction with evidence-based medicine and healthcare policy, developing adjuvant therapy strategies for breast cancer following neoadjuvant therapy has the benefit of providing more precise treatment options for patients.

Maxillofacial trauma caused by e-scooters: a retrospective review prior to the extension of the UK scheme.

The nationwide extension of the electric scooter (e-scooter) scheme, which began in 2020, aimed to alleviate public transport congestion, to reduce pollution and peak-time road traffic. This retrospective study evaluates the range of e-scooter-related maxillofacial trauma before the recent scheme extension and compares the findings with existing literature on this topic. The Queen Elizabeth Hospital Birmingham, United Kingdom (UK) operates as a Level 1 Regional Major Trauma Centre and serves a population of four million. All patient records between September 2021 to September 2022 were analysed to establish the types of e-scooter-related maxillofacial trauma sustained. A Pearson's chi-squared test was used to assess for significant associations between variables recorded. Falls accounted for the majority of injuries (44.3%), and soft tissue lacerations were the most common maxillofacial injury (38%). Statistically significant results were measured in the following variables: gender and intoxication status (p = 0.007), helmet status and injuries sustained in maxillofacial and non-maxillofacial regions (p = 0.043), mechanism of injury and injuries sustained in both the maxillofacial and non-maxillofacial regions (p = 0.045). E-scooters are an emerging concern within the UK. Further studies across the UK are required to assess the frequency of e-scooter-related injuries. Such data may prove useful in determining the government's decision on e-scooter use on UK roads.

Remnant cholesterol is associated with hip BMD and low bone mass in young and middle-aged men: a cross-sectional study.

PURPOSE: Remnant cholesterol (RC) is a contributor to cardiovascular diseases, obesity, diabetes, and metabolic syndrome. However, the specific relationship between RC and bone metabolism remains unexplored. Therefore, we aimed to investigate the relationships of RC with hip bone mineral density (BMD) and the risk of low bone mass. METHODS: Physical examination data was collected from men aged < 60 years as part of the Kailuan Study between 2014 and 2018. The characteristics of the participants were compared between RC quartile groups. A generalized linear regression model was used to evaluate the relationship between RC and hip BMD and a logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for low bone mass. Additional analyses were performed after stratification by body mass index (BMI) (≥ or < 24 kg/m2). Sensitivity analyses were performed by excluding individuals who were taking lipid-lowering therapy or had cancer, cardiovascular diseases, or diabetes. RESULTS: Data from a total of 7,053 participants were included in the analysis. After adjustment for confounding factors, RC negatively correlated with hip BMD (ß = - 0.0079, 95% CI: - 0.0133, - 0.0025). The risk of low bone mass increased from the lowest to the highest RC quartile, with ORs of 1 (reference), 1.09 (95% CI: (0.82, 1.44), 1.35 (95%CI: 1.02, 1.77), and 1.43 (95% CI: 1.09, 1.89) for Q1, Q2, Q3, and Q4, respectively (P for trend = 0.004) in the fully adjusted model. Compared to RC < 0.80 mmol/l group, the risk of low bone mass increased 39% in RC ≥ 0.80 mmol/l group (P < 0.001). The correlation between RC and hip BMD was stronger in participants with BMI ≥ 24 kg/m2 group (ß = - 0.0159, 95% CI: - 0.0289, - 0.0029). The results of sensitivity analyses were consistent with the main results. CONCLUSION: We have identified a negative correlation between serum RC and hip BMD, and a higher RC concentration was found to be associated with a greater risk of low bone mass in young and middle-aged men.

[Advances in oncolytic virotherapy for glioma].

In recent years, there has been significant progress in the research of oncolytic viruses for the therapy of gliomas. The latest clinical trial results related to the modification, effectiveness, and safety of oncolytic viruses have brought hope for the development of glioblastoma treatments. Modified oncolytic viruses, particularly those based on the herpes simplex virus, have gained approval in Japan. Clinical trials involving recombinant poliovirus have shown better-than-expected survival outcomes with a strong safety profile. Notably, the first-time report of adenovirus in combination with immune checkpoint inhibitors for glioblastoma has demonstrated promising survival benefits and safety. However, challenges remain, including the selection of administration routes and the sustainability of treatment effects during oncolytic virus therapy. Therefore, further preclinical and clinical studies are required to improve the effectiveness and optimize treatment strategy for glioblastoma using oncolytic viruses.

Survival Outcomes and Patterns of Care for Stage II or III Resected Gastric Cancer by Race and Ethnicity.

Importance: Many multimodality treatment regimens exist for gastric adenocarcinoma, including neoadjuvant vs adjuvant chemotherapy, radiation, or both. Neoadjuvant therapy is recommended in the United States for patients with locally advanced gastric cancer; however, it is unknown whether the outcomes of neoadjuvant therapy are associated with race and ethnicity. Objective: To evaluate the differences in outcomes by race and ethnicity of patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy. Design, Setting, and Participants: This retrospective cohort study examined the National Cancer Database from the American College of Surgeons for patients with clinical stage II or III gastric adenocarcinoma, excluding gastric cardia tumors, undergoing surgical resection procedures from January 2006 to December 2019. Statistical analysis was performed from December 2021 to May 2023. Exposure: Patients were stratified by race and ethnicity, and their outcomes were analyzed for those who received and did not receive neoadjuvant therapy. Main Outcomes and Measures: The Cox proportional hazard model was used to compare overall survival (OS) between racial and ethnic groups (Asian, Black, Hispanic, and White) overall and according to receipt of neoadjuvant therapy. Among those who received neoadjuvant therapy, proportional differences in pathological responses were calculated in each group. Results: Among a total of 6938 patients in the cohort, 4266 (61.4%) were male; mean (SD) age was 65.9 (12.8) years; 1046 (15.8%) were Asian, 1606 (24.3%) were Black, 1175 (17.8%) were Hispanic, and 3540 (53.6%) were White. Compared with other races and ethnicities, the group of White patients had significantly more who were 65 years or older with more comorbidities. White patients underwent surgical resection procedures alone without neoadjuvant or adjuvant therapy more frequently than other races and ethnicities. Asian and Black patients had the highest proportion of being downstaged or achieving pathological complete response after neoadjuvant therapy. In multivariate models, perioperative chemotherapy was associated with improved OS (HR, 0.79 [95% CI, 0.69-0.90]), whereas number of positive lymph nodes and surgical margins were associated with the largest decreases in OS. Asian and Hispanic race and ethnicity were associated with significantly improved OS compared with Black and White races (eg, Asian patients: HR, 0.64 [95% CI, 0.58-0.72]; and Hispanic patients: HR, 0.77 [95% CI, 0.69-0.85]). Black race was associated with improved OS compared with White race when receiving neoadjuvant therapy (HR, 0.78 [95% CI, 0.67-0.90]). Conclusions and Relevance: In this large nationwide cohort study of survival outcomes among patients with resected clinical stage II or III gastric cancer, there were significant differences in response to treatment and OS between different racial and ethnic groups.

[Expression level of Wilms' tumor 1 gene and its correlation with clinical features in patients with myeloproliferative neoplasms].

Objective: To investigate the expression level of WT1 gene in patients with classical Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) and its correlation with clinical features. Methods: A retrospective study included 252 patients with newly diagnosed MPN in Zhongnan Hospital of Wuhan University from January 2015 to March 2023, including 128 males and 124 females, aged［M（Q1，Q3）］62 (53, 69) years. The WT1-positive group (n=93) and the WT1-negative group (n=159) were split based on the level of WT1 gene expression, and the variations in clinical indicators between the two groups were compared. Its levels of expression in each subtype and its relationships to thrombotic events and clinically significant variables were analyzed. As of March 31, 2023, the follow-up period [M (Q1, Q3)] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis. Results: The WT1 gene expression level in the overall bone marrow samples of 252 patients with newly diagnosed MPN was 0.30% (0.10%, 1.10%). The expression level in primary myelofibrosis (PMF) patients was 1.45% (0.41%, 3.24%), which was higher than 0.15% (0.02%, 0.32%), 0.37% (0.16%, 1.09%) in essential thrombocythemia (ET) and polycythemia vera (PV) patients (both P<0.05). Positive correlations were found between WT1 gene expression levels and JAK2V617F gene mutation load, RDW, MPV (r=0.478, 0.346, 0.236, all P<0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (r=-0.339, -0.170, -0.206, -0.388, all P<0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2V617F gene mutation, and higher levels of RDW, LDH, NEUT, and MPV compared to the WT1-negative group. In contrast, the proportion of triple-negative (negative for all three hot mutations of JAK2V617F, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all P<0.05). The thrombotic event rates of WT1-positive group and WT1-negative group were 32.3% (30/93) and 32.1% (51/159), respectively, and the difference was not statistically significant (P=0.883). Logistic regression analysis showed that male (OR=2.41,95%CI:1.02-5.71,P=0.046) and positive JAK2V617F gene mutation (OR=3.96,95%CI:1.50-10.42,P=0.005) were risk factors for thrombotic events in ET patients. Conclusions: WT1 gene expression is elevated in PMF patients and correlated with indicators of disease progression and transformation in MPN patients. It can be utilized as an auxiliary diagnostic indicator for classical MPN staging but is not correlated with the incidence of thrombotic events. Male and positive JAK2V617F gene mutation are risk factors for thrombotic events in ET patients.

[Associations between risk factor control and survival among cancer patients].

Objective: This study aimed to evaluate the associations between the number of cardiovascular risk factor goals achieved with all-cause mortality, atherosclerotic cardiovascular diseases (ASCVD)-related mortality, and cancer-related mortality amongst cancer patients. Methods: From 2006 to 2020, a total of 2 079 individuals with newly diagnosed cancer, free of ASCVD, were enrolled in this study from the Kailuan cohort. Patients were classified into three groups (group 1,≤1 risk factor at goal, n=407; group 2, 2 risk factors at goal, n=865; group 3,≥3 risk factors at goal, n=807) according to the control status of blood pressure, fasting blood glucose, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, using health checkup results of the latest survey after cancer diagnosis. Multivariable Cox regression analyses were performed to examine the associations between the number of risk factors at goals with all-cause mortality, ASCVD-related mortality, and cancer-related mortality. Results: The mean age at diagnosis was (60.4±10.4) years, and 71.2% were male. During a median follow-up of 2.95 (1.38, 5.12) years, 600 cases of all-cause mortality, 63 cases of ASCVD-related mortality, and 314 cases of cancer-related mortality were observed. After adjusting for age, gender, education level, smoking status, alcohol consumption, salt intake, physical activity, body mass index, triglyceride, high-density lipoprotein cholesterol, family history of cardiovascular diseases, antihypertensive drugs, hypoglycemic drugs, lipid-lowering drugs, and anti-cancer medications, compared with cancer patients achieving ≤1 risk factor goal, those achieving ≥3 risk factor goals showed significantly decreased risk of all-cause mortality, ASCVD mortality, and cancer mortality, with HR (95%CI) of 0.68 (0.54-0.86), 0.35 (0.16-0.77), and 0.60 (0.43-0.82), respectively (all P values <0.05). Significant relationships between the number of risk factor goals achieved and decreased mortality of all kinds were observed (all P values for trend<0.05). Results of the subgroup analyses suggested that the associations between the number of risk factor goals achieved and lower mortality of all kinds were more prominent among individuals who were ≥60 years, male, and those with respiratory and reproductive cancers (all P values <0.05). Conclusions: This study suggested a significant association between the number of cardiovascular risk factor goals achieved and survival in cancer patients, especially amongst those who were older, male, with respiratory cancers and reproductive cancers.

Clinical efficacy and safety of adjuvant immunotherapy (Tislelizumab) plus chemotherapy vs. adjuvant chemotherapy alone in lymph node-positive patients with gastric cancer after D2 radical resection: a prospective, 2-arm, phase II study.

OBJECTIVE: This study aims to investigate the effectiveness and safety of adjuvant Tislelizumab (BeiGene China Co., Ltd, Changping District, Beijing, China) in combination with chemotherapy for patients with localized lymph node-positive disease following D2 (extended lymphadenectomy) radical gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients with lymph node-positive gastric cancer who underwent D2 radical gastrectomy at Yixing People's Hospital between April 2021 and June 2022 were selected and enrolled in the study. They were divided into the study group, which received immunotherapy (Tislelizumab) in combination with chemotherapy (XELOX regimen: Xeloda plus Oxaliplatin), or the control group, which received chemotherapy alone (XELOX regimen). Adverse events, disease-free survival (DFS), and overall survival (OS) were observed. This study was registered on ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT05844371). RESULTS: The one-year disease-free survival (DFS) rate was 81.82% in the study group compared to 71.43% in the control group. Although the DFS rate tended to be higher in the study group, the difference did not reach statistical significance (p=0.388, HR=0.573, 95% CI: 0.161-2.032). Patients in both groups tolerated the treatment well. Both groups exhibited similar rates of neutropenia, hemoglobin depletion, gastrointestinal reactions, abnormal liver function, and peripheral neuritis. The majority of adverse events in both groups were grade 1-2, with only hypothyroidism showing a significant difference (p=0.021). The only statistically significant difference in grade 3-4 adverse events was thrombocytopenia (p=0.048). All adverse reactions were effectively managed with symptomatic treatment. CONCLUSIONS: The addition of adjuvant PD-1 inhibitor (Tislelizumab) to XELOX therapy showed a favorable impact on the one-year disease-free survival (DFS) rate when compared to adjuvant XELOX chemotherapy alone in patients with regional lymph node-positive disease after D2 radical gastrectomy. Moreover, patients were able to tolerate the accompanying adverse effects, which were deemed safe.

[Research progress on the role of adipose-derived stem cell exosomes in skin scar formation].

The adipose-derived stem cell exosomes are subcellular structures of adipose stem cells. They are nano-sized membrane vesicles that can transport various cell components and act on target cells by paracrine, and they play an important role in the exchanges of substance and information between cells. Scar healing is the commonest way of healing after skin tissue injury. Pathological scar can not only cause movement dysfunction, but also lead to deformity, which affects the appearance of patients and brings life and mental pressure to the patients. In recent years, many researches have shown that the adipose-derived stem cell exosomes contain a variety of bioactive molecules, which play an important role in reducing scar formation and scar-free wound healing, by affecting the proliferation and migration of fibroblasts and the composition of extracellular matrix. This article reviewed the recent literature on the roles and mechanisms of adipose-derived stem cell exosomes in scar formation, and prospected the future application and development of adipose-derived stem cell exosomes in scar treatment.

Knockdown of Long Noncoding RNA CCAT2 Suppresses Malignant Phenotype in Human Laryngeal Squamous Cell Carcinoma.

This study aimed to explore the biological role and mechanism underlying the effects of colon cancer-associated transcript 2 (CCAT2), a long noncoding RNA (lncRNA) in human laryngeal squamous cell carcinoma (LSCC). CCAT2 expression levels in clinical LSCC samples and TU-212 cell line were evaluated by quantitative real-time PCR. The correlation of CCAT2 expression level with clinical-pathological characteristics of patients and their prognosis was analyzed. The functional role of CCAT2 in human LSCC was assessed by Cell Counting Kit-8, Transwell assay, flow cytometric analysis, and LSCC xenograft experiment in vivo. The expression of potential targeted proteins was detected by Western blotting and immunohistochemistry. We found that expression of CCAT2 was significantly elevated in LSCC tissues and TU-212 cells (p<0.05). Survival analysis showed that LSCC patients with high expression of CCAT2 had a shorter 5-year overall survival rate than those with low expression (p<0.05). In addition, CCAT2 silencing with short hairpin RNA significantly decreased the proliferative and invasive potential of TU-212 cells (p<0.05) and promoted their apoptosis. In Nude mice, CCAT2 knockdown suppressed the growth of tumor and decreased its volume and weight in comparison with the controls (p<0.05). In TU-212 cells, CCAT2 silencing with short hairpin RNA significantly down-regulated the expression of ß-catenin and CDK8 (p<0.05). Thus, knockdown of CCAT2 suppresses proliferation and invasion of the cells and inhibits Wnt/ß-catenin signaling pathway in LSCC, which indicates novel therapeutic targets and prognostic indicators in patients with LSCC.

CLDN6 Suppresses Migration and Invasion of MCF-7 and SKBR-3 Breast Cancer Cells by Blocking the SMAD/Snail/MMP-2/9 Axis.

The study examined the mechanisms of action of signal protein claudin 6 (CLDN6) on migration and invasion of breast cancer cell lines MCF-7 and SKBR-3. To this end, the signal proteins SMAD were blocked with their inhibitor SB431542, the genes CLDN6 and SNAIL were knocked down with short hairpin RNAs, and MMP2 and MMP9 were inhibited with TIMP-1. Expressions of MMP2 and MMP9 mRNAs were evaluated by reverse transcription PCR, Expressions of MMP-2, MMP-9, E-cadherin, N-cadherin, and vimentin were examined by Western blotting. Migration and invasion were analyzed by scratch test and Matrigel invasion assay. SB431542 inhibited expression of MMP2 and MMP9 in both cell lines. Single use of SB431542 inhibited expression of MMP-2/MMP-9 and corresponding mRNAs, but subsequent silencing of CLDN6 gene reversed this effect. TIMP-1 reversed down-regulation of E-cadherin, upregulation of N-cadherin and vimentin, facilitation of migration and invasion evoked by CLDN6 knocking down. Silencing of SNAIL gene inhibited migration and invasion, upregulated the expression of E-cadherin, and down-regulated expression of MMP2, MMP 9, N-cadherin, and vimentin. Thus, CLDN6 suppresses the epithelial-mesenchymal transition, migration, and invasion via blocking SMAD/Snail/MMP-2/9 signaling pathway in MCF-7 and SKBR-3 cancer cell lines.