Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Clinical Application of Bilateral Nasopharyngeal Airway in Painless Colonoscopy for Obese Patients.

Objective: This study aims to evaluate the safety and efficacy of using bilateral nasopharyngeal airways (NPA) during colonoscopic polypectomy performed under sedation anesthesia in obese patients. Methods: Ninety obese patients undergoing colonoscopic polypectomy under elective sedation anesthesia at Shanghai Shuguang Hospital were randomly allocated to two groups. Patients in group B had a nasopharyngeal airway inserted bilaterally after induction of anesthesia, whereas patients in group U had a nasopharyngeal airway inserted in only one nostril. Spontaneous breathing was maintained in both groups. The primary observation parameter was the incidence of oxygen saturation (SpO2) ≤ 92% during anesthesia, while secondary observation parameters included preoperative, intraoperative, and post-operative SpO2 levels, mean arterial pressure (MAP), heart rate (HR), dosage of propofol, duration of the operation, time to anesthesia recovery, need for emergency airway intervention, and occurrence of other adverse events. Results: Hypoxia occurred in 5 out of 45 patients (11.1%) in group B, whereas it was observed in 14 out of 45 patients (31.1%) in group U (P < 0.05). Patients in group B exhibited higher SpO2 levels during and after surgery compared to those in group U (P < 0.05). Furthermore, the decrease in intraoperative and post-operative SpO2 levels from baseline was significantly lower in group B compared to group U (P < 0.05). The number of emergency airway interventions, operation time, propofol dosage, and anesthesia recovery time were significantly lower in group B compared to group U (P < 0.05). However, there were no significant differences in MAP, HR, or the incidence of adverse events between the two groups (P > 0.05). Conclusion: The utilization of bilateral nasopharyngeal airway placement proves to be an effective strategy in decreasing the occurrence of hypoxia among obese patients undergoing colonoscopy under sedation anesthesia, thereby improving procedural safety.

Profiles of peripheral B cell subsets in a cohort of primary Sjögren's syndrome patients and their potential clinical significance.

Background/purpose: Primary Sjögren's syndrome is a prototypical autoimmune disease, with B cell dysfunction as a dominant feature. Further insights into distribution of B cell subsets in primary Sjögren's syndrome are urgently required to identify the most appropriate target subpopulation. We aimed to evaluate the profiles of B lymphocyte subpopulations in primary Sjögren's syndrome patients and to investigate their clinical significance. Materials and methods: Thirty primary Sjögren's syndrome patients and 15 age-and sex-matched healthy controls were recruited. Peripheral B cell subsets were analyzed by flow cytometry. Results: Compared to healthy controls, circulating CD19+ B cells, CD19+CD20- B cells, CD19+CD27-IgD+ naïve B cells, CD19+IgD+CD38high plasmablasts, CD19+CD24highCD38high transitional B cells and CD19+CD20-CD27+CD38+ plasma cells were elevated in patients with primary Sjögren's syndrome, whereas CD19+CD27+ memory B cells, CD19+CD27-IgD- double negative B cells and CD19+CD24hiCD27+ Bregs were decreased. Furthermore, the percentage of circulating CD19+CD20-CD27+CD38+ plasma cells was positively correlated with serum IgG levels and the proportional area of lymphocytic infiltration of labial gland. Conclusion: We identified a comprehensive B lymphocyte subset distribution profile in primary Sjögren's syndrome. Moreover, we detected a clinical significance of CD19+CD20-CD27+CD38+ plasma cells, suggesting that these cells might play a key role in disease pathology and represent potential therapeutic targets.

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma.

Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate the oncogenic role of PLD1, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA, which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression markedly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, substantially inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

Clinical, histopathological characteristics and malignant transformation of proliferative verrucous leukoplakia with 36 patients: a retrospective longitudinal study.

BACKGROUND: Proliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL. METHODS: This study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients. RESULTS: The cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan-Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05). CONCLUSION: The main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.

TAAR1 in dentate gyrus is involved in chronic stress-induced impairments in hippocampal plasticity and cognitive function.

Multiple lines of evidence suggest that the trace amine-associated receptor 1 (TAAR1) holds promise as a potential target for stress-related disorders, such as treating major depressive disorder (MDD). The role of TAAR1 in the regulation of adult neurogenesis is recently supported by transcriptomic data. However, it remains unknown whether TAAR1 in dentate gyrus (DG) mediate chronic stress-induced negative effects on hippocampal plasticity and related behavior in mice. The present study consisted of a series of experiments using RNAscope, genetic approaches, behavioral tests, immunohistochemical staining, Golgi-Cox technique to unravel the effects of TAAR1 on alterations of dentate neuronal plasticity and cognitive function in the chronic social defeat stress model. The mice subjected to chronic defeat stress exhibited a noteworthy decrease in the mRNA level of TAAR1 in DG. Additionally, they exhibited compromised social memory and spatial object recognition memory, as well as impaired proliferation and maturation of adult-born dentate granule cells. Moreover, the selective knockout TAAR1 in DG mostly mimicked the cognitive function deficits and neurogenesis impairment induced by chronic stress. Importantly, the administration of the selective TAAR1 partial agonist RO5263397 during stress exposure attenuated the adverse effects of chronic stress on cognitive function, adult neurogenesis, dendritic arborization, and the synapse number of dentate neurons in DG. In summary, our findings suggest that TAAR1 plays a crucial role in mediating the detrimental effects of chronic stress on hippocampal plasticity and cognition. TAAR1 agonists exhibit therapeutic potential for individuals suffering from cognitive impairments associated with MDD.

Randomized Controlled Trial Investigating the Impact of High-Flow Nasal Cannula Oxygen Therapy on Patients Undergoing Robotic-Assisted Laparoscopic Rectal Cancer Surgery, with a Post-Extubation Atelectasis as a Complication.

Background: Utilizing high-flow nasal cannula (HFNC) oxygen therapy may prevent the collapse of alveoli and improve overall alveolar ventilation. In this study, we aimed to investigate the impact of HFNC on postoperative atelectasis in individuals undergoing robotic-assisted laparoscopic surgery. Methods: Patients undergoing robotic-assisted laparoscopic surgery for rectal cancer were randomly assigned to the control or HFNC groups. After the surgical procedure was complete and the trachea was extubated, both groups underwent an initial lung ultrasound (LUS) scan. In the post-anesthesia care unit (PACU), the control group received conventional nasal cannula oxygen therapy, while the HFNC group received high-flow nasal cannula oxygen therapy. A second LUS scan was conducted before the patient was transferred to the ward. The primary outcome measured was the total LUS score at the time of PACU discharge. Results: In the HFNC group (n = 39), the LUS score and the incidence of atelectasis at PACU discharge were significantly lower compared to the control group (n = 39) [(5 vs 10, P < 0.001), (48.72% vs 82.05%, P = 0.002)]. None of the patients in the HFNC group experienced hypoxemia in the PACU, whereas six patients in the control group did (P = 0.03). Additionally, the minimum SpO2 value in the PACU was notably higher in the HFNC group compared to the control group [99 vs 97, P < 0.001]. Conclusion: Based on the results, HFNC improves the extent of postoperative atelectasis and decreases the occurrence of atelectasis in individuals undergoing robotic-assisted laparoscopic surgery for rectal cancer.

NRAMP6c plays a key role in plant cadmium accumulation and resistance in tobacco (Nicotiana tabacum L.).

Tobacco plants (Nicotiana tabacum L.) exhibit considerable potential for phytoremediation of soil cadmium (Cd) pollutants, owing to their substantial biomass and efficient metal accumulation capabilities. The reduction of Cd accumulation in tobacco holds promise for minimizing Cd intake in individuals exposed to cigar smoking. NRAMP transporters are pivotal in the processes of Cd accumulation and resistance in plants; however, limited research has explored the functions of NRAMPs in tobacco plants. In this investigation, we focused on NtNRAMP6c, one of the three homologs of NRAMP6 in tobacco. We observed a robust induction of NtNRAMP6c expression in response to both Cd toxicity and iron (Fe) deficiency, with the highest expression levels detected in the roots. Subsequent subcellular localization and heterologous expression analyses disclosed that NtNRAMP6c functions as a plasma membrane-localized Cd transporter. Moreover, its overexpression significantly heightened the sensitivity of yeast cells to Cd toxicity. Through CRISPR-Cas9-mediated knockout of NtNRAMP6c, we achieved a reduction in Cd accumulation and an enhancement in Cd resistance in tobacco plants. Comparative transcriptomic analysis unveiled substantial alterations in the transcriptional profiles of genes associated with metal ion transport, photosynthesis, and macromolecule catabolism upon NtNRAMP6c knockout. Furthermore, our study employed plant metabolomics and rhizosphere metagenomics to demonstrate that NtNRAMP6c knockout led to changes in phytohormone homeostasis, as well as shifts in the composition and abundance of microbial communities. These findings bear significant biological implications for the utilization of tobacco in phytoremediation strategies targeting Cd pollutants in contaminated soils, and concurrently, in mitigating Cd accumulation in tobacco production destined for cigar consumption.

Branched-chain amino acids promote occurrence and development of cardiovascular disease dependent on triglyceride metabolism via activation of the mTOR/SREBP-1/betatrophin pathway.

Branched-chain amino acid (BCAA) metabolism is associated with triglyceride (TG) metabolism and the development of cardiovascular disease (CVD). However, the underlying mechanism remains uncertain. This study included 1302 subjects and followed for 4-5 years. A hyperbranched-chain aminoacidemia rat model was induced by high fructose diet (HFTD). The relationship between BCAAs and TG level and its regulatory mechanism was investigated in vitro. As results, as baseline BCAA percentile increased, subjects had higher prevalence and incidence of T2DM, NAFLD, and CVD risk (P < 0.05). In animal model, the accumulation of BCAAs and TG and betatrophin expression were significantly elevated in the HFTD group when comparing with those in the SD group(P < 0.05). Immunofluorescence and Masson's trichrome staining revealed that the area of interstitial fibrosis was significantly increased in the HFTD group compared with control group. Met treatment significantly decreased TG levels and betatrophin expression and reversed myocardial fibrosis (P < 0.05). In vitro, LO2 cells, stimulated with 0.1-5 mM BCAAs, displayed a significant dose-dependent increase in betatrophin expression (P < 0.05). And 5 mM BCAAs stimulation significantly increased the p-mTOR and SREBP-1 expression (P < 0.05). However, this effect could be reversed by using the corresponding inhibitor or siRNAs. In conclusions, BCAAs promote occurrence and development of cardiovascular disease dependent on TG metabolism via activation of the mTOR/SREBP-1/betatrophin pathway. The study provides a new theory for the pathogenesis of CVD caused by amino acid metabolism disorders.

Construction and effect of a high glucose induced hippocampal neuron metabolic memory cell model in HT-22 mice / 天津医药

Objective To construct an in vitro"metabolic memory"cell model of HT-22 mouse hippocampal neurons induced by high glucose,and to investigate the effect of"metabolic memory"on apoptosis and histone acetylation in HT-22 cells.Methods HT-22 cells were cultured in high glucose medium(glucose concentration was 55 mmol/L)and conventional glucose medium(glucose concentration was 25 mmol/L),and cells were divided into the control group(NG 4,6 and 8 groups,25 mmol/L glucose was cultured for 4,6 and 8 days,respectively),the high glucose group(HG 4,6 and 8 groups,respectively)and the metabolic memory group(HG2NG2,HG2NG4,HG2NG6,HG4NG2 and HG4NG4 groups,high glucose culture for 2 days to 25 mmol/L glucose culture for 2,4 or 6 days,high glucose culture for 4 days to 25 mmol/L glucose culture for 2 or 4 days).Cell viability was detected by CCK-8 method.The release of lactate dehydrogenase(LDH)in cell culture supernatant was detected,and the optimal time to establish a"metabolic memory"model was selected.Subsequently,cells were divided into the NG4 group,the NG8 group,the HG4 group,the HG4NG4 group and the HG8 group,and the cell morphology of each group was observed by optical microscope.The apoptosis rate was detected by flow cytometry.The activities of deacetylase(HDAC)and histone acetyltransferase(HAT)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot assay was used to detect expression levels of histone deacetylase 4(HDAC4),B lymphocyte tumor 2(Bcl-2),Bcl-2 related X protein(Bax)and Caspase-3 protein.Results The HG4NG4 group was the ideal cell model with high glucose metabolic memory.Cells of the NG4 group and the NG8 group were interwoven into a dense network,growing well,with spindle shaped cells and distinct synaptic structures.However,in the HG4 group and the HG8 group,the cell body became round,synaptic structure disappeared and growth was inhibited.In the HG4NG4 group,the number of cells increased but their morphology was damaged.Results of flow cytometry showed that compared with the NG8 group,the apoptosis rates were significantly increased in the HG8 group and the HG4NG4 group(P＜0.05).ELISA results showed that compared with the NG8 group,the expression levels of HDAC4,Bax,and Caspase-3 proteins increased in the HG8 group and the HG4NG4 group,while the expression level of Bcl-2 protein significantly decreased(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels of HAT and HDAC in the HG4NG4 group.Western blot reslts showed that compared with the NG8 group,the levels of HDAC4,Bax and Caspase-3 protein increased in the HG8 group and the HG4NG4 group(P＜0.05).Compared with the HG8 group,there were no significant differences in protein expression levels in the HG4NG4 group.Conclusion HT-22 mouse hippocampal neurons cultured with 55mmol/L high glucose for 4 days,and then cultured with 25 mmol/L glucose for 4 days are the ideal"metabolic memory"cell model.The mechanism may be related to the increased activity of HDAC,HAT and HDAC4 expression in the hyperglycemic model.

Therapeutic efficacy of automatic peritoneal dialysis on elderly patients with cardiorenal syndrome / 中华老年心脑血管病杂志

Objective To explore the therapeutic efficacy of automatic peritoneal dialysis on elderly patients with cardiorenal syndrome(CRS).Methods A total of 260 elderly CRS patients treated at our hospital from January 2019 to January 2022 were recruited,and then randomly divided into an observation group and a control group,with 130 cases in each group.The control group received conventional basic treatment and symptomatic treatment,while the observation group received automated peritoneal dialysis treatment on this basis.Cardiac function indicators,renal function indicators,inflammatory factors,MAP and heart rate were compared between the two groups.Re-sults After treatment,significantly lower LVESD(26.29±1.19 mm vs 29.59±1.84 mm),LVEDD(47.43±1.39 mm vs 51.81±1.34 mm),LAD(30.74±1.15 mm vs 33.11±0.88 mm),and levels of NT-proBNP(1034.74±313.61 ng/L vs 2634.02±853.67 ng/L),urea(16.69±3.57 mmol/L vs 32.67±4.54 mmol/L),cystatin C(0.47±0.13 mg/L vs 0.61±0.15 mg/L),creatinine(254.74±41.15 mmol/L vs 394.09±38.61 mmol/L),TNF-α(144.14±23.16 mg/L vs 183.97± 23.37 mg/L)and hs-CRP(4.09±1.03 μg/L vs 5.45±1.17 μg/L),and higher LVEF(39.14± 4.48％vs 35.64±5.27％)were observed in the observation group than the control group(all P＜0.01).There were no significant differences in heart rate and MAP between the two groups before and after treatment(P＞0.05).Conclusion Automatic peritoneal dialysis can improve the cardiac and renal function and reduce inflammatory response in elderly CRS patients,and show positive significance for improving prognosis.

Budd-Chiari syndrome with hepatopulmonary syndrome: a case report and literature review / 中华儿科杂志

Objective: To summarize the clinical features and prognosis of Budd-Chiari syndrome with hepatopulmonary syndrome (HPS) in children. Methods: The clinical data of a child who had Budd-Chiari syndrome with HPS treated at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in December 2016 was analyzed retrospectively. Taking "Budd-Chiari syndrome" and "hepatopulmonary syndrome" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2023. Combined with this case, the clinical characteristics, diagnosis, treatment and prognosis of Budd-Chiari syndrome with HPS in children under the age of 18 were summarized. Results: A 13-year-old boy, presented with cyanosis and chest tightness after activities for 6 months, and yellow staining of the skin for 1 week. Physical examination at admission not only found mild yellow staining of the skin and sclera, but also found cyanosis of the lips, periocular skin, and extremities. Laboratory examination showed abnormal liver function with total bilirubin 53 μmol/L, direct bilirubin 14 μmol/L, and indirect bilirubin 39 μmol/L, and abnormal blood gas analysis with the partial pressure of oxygen of 54 mmHg (1 mmHg=0.133 kPa), the partial pressure of carbon dioxide of 31 mmHg, and the alveolar-arterial oxygen gradient of 57 mmHg. Hepatic vein-type Budd-Chiari syndrome, cirrhosis, and portal hypertension were indicated by abdominal CT venography. Contrast-enhanced transthoracic echocardiography (CE-TTE) was positive. After symptomatic and supportive treatment, this patient was discharged and received oxygen therapy outside the hospital. At follow-up until March 2023, there was no significant improvement in hypoxemia, accompanied by limited daily activities. Based on the literature, there were 3 reports in English while none in Chinese, 3 cases were reported. Among a total of 4 children, the chief complaints were dyspnea, cyanosis, or hypoxemia in 3 cases, and unknown in 1 case. There were 2 cases diagnosed with Budd-Chiari syndrome with HPS at the same time due to respiratory symptoms, and 2 cases developed HPS 1.5 years and 8.0 years after the diagnosis of Budd-Chiari syndrome respectively. CE-TTE was positive in 2 cases and pulmonary perfusion imaging was positive in 2 cases. Liver transplantation was performed in 2 cases and their respiratory function recovered well; 1 case received oxygen therapy, with no improvement in hypoxemia; 1 case was waiting for liver transplantation. Conclusions: The onset of Budd-Chiari syndrome with HPS is insidious. The most common clinical manifestations are dyspnea and cyanosis. It can reduce misdiagnosis to confirm intrapulmonary vascular dilatations with CE-TTE at an early stage. Liver transplantation is helpful in improving the prognosis.

The Uptake and Distribution Evidence of Nano- and Microplastics in vivo after a Single High Dose of Oral Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.@*METHODS@#Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.@*RESULTS@#In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.@*CONCLUSION@#Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs.

Application and diagnostic value of low dose scan technique of chest CT combined with 3D reconstruction for ribs in chest trauma / 中国医学装备

Objective:To explore the application and diagnostic value of low-dose scan technique of chest computed tomography(CT)combined with three dimensional(3D)reconstruction for ribs in chest trauma.Methods:A total of 118 patients with highly suspected rib fracture who admitted to the 904th Hospital of People's Liberation Army Joint Service Support Force were selected,and all cases underwent low-dose scan technique of chest CT combined with 3D reconstruction for ribs.The image qualities of chest CT scans with different low-doses combined with 3D reconstruction for ribs were analyzed,and the diagnostic accuracies among low dose scan technique of chest CT,3D reconstruction for ribs and the combination of them for chest trauma were compared.Results:Both the sharpness and clarity of the edges of the bronchi,blood vessels,lung parenchyma,interlobular septum,mediastinum and ribs were poorer,and the artifacts of soft tissue were more and the noise were more when the tube current of CT scan was 50 Ma.Both the sharpness and clarity of the edges of the bronchi,blood vessels,lung parenchyma,interlobular septum,mediastinum and ribs were general,and a part of soft tissues existed artifacts and the noise amounts were less when the tube current of CT scan was 70 Ma,which did not affect the diagnosis.The radiation dose as 50 mA was significantly higher than that as 70 mA,with a statistically significant difference(t=10.969,P<0.05).In 118 patients with chest trauma,the examination of low-dose scan technique of chest CT combined with 3D reconstruction for ribs indicated that there were 112 cases of rib fractures and 7 cases of costal cartilage fractures.In the examined 388 fractures of rib and costal cartilage,355 fractures(91.49%)were rib fractures and 33 fractures(8.51%)were costal cartilage fractures.In 118 patients with chest trauma,76 cases(64.41%)complicated with pulmonary contusions and lacerations,and 41 cases(35.75%)complicated with pleural effusion,and 10 cases(8.47%)complicated with thoracic vertebral fractures,and 6 cases(5.08%)complicated with splenic contusions and lacerations,and 5 cases(4.24%)complicated with mediastinal and subcutaneous emphysemas.The most direct imaging sign of rib fracture was visible and transparent low-density shadow.Chest CT scan can generally better display dislocation of the fractured end.The 3D reconstruction image showed a visibly line-like shadow on one side of rib if only one side of ribs fractured and the other side was intact.A total of 395 rib and costal cartilage fractures were confirmed by 3D reconstruction,which included 363 rib fractures(91.90%)and 32 costal cartilage fractures(8.10%).A total of 410 rib and costal cartilage fractures were confirmed by low-dose scan technique of chest CT combined with 3D reconstruction for ribs,which included 375 rib fractures(91.46%)and 35 costal cartilage fractures(8.54%).In the comparison of 418 rib injuries that were confirmed during surgery,the accuracy of low-dose scan technique of chest CT was 92.82%(388/418)in diagnosing rib and costal cartilage fractures,and the accuracy of 3D reconstruction for ribs was 94.50%(395/418)in diagnosing that,and the accuracy of low-dose scan technique of chest CT combined with 3D reconstruction for ribs was 95.69%(410/418)in diagnosing that.There was a significant difference in accuracy among the three types of examinations(x2=13.062,P<0.05).Conclusion:Low dose scan technique of chest CT combines with 3D reconstruction for ribs can be used in the diagnosis of chest trauma,which has higher accuracy and can provide reliable imaging information for clinical diagnosis and treatment.

Efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention in patients with coronary artery disease: a meta-analysis.

Background: The benefits and risks of aspirin verse clopidogrel monotherapy in patients with coronary artery disease (CAD) remain controversial. This meta-analysis evaluated the efficacy and safety of aspirin verse clopidogrel monotherapy for long-term treatment in patients with CAD. Methods: Literature was searched in the Pubmed, the Cochrane Library, and the Embase databases until March 2023. The Cochrane Risk of Bias Tool was used to assess the risk of bias in included studies. Data were extracted from the included studies, heterogeneity analysis, and pooled analysis conducted by RevMan 5.3 software. Results: A total of five trials were included, involving 11, 766 patients with CAD. Compared with the aspirin group, the clopidogrel group was associated with reduced risk of major adverse cardiac and cerebrovascular events (MACCE) [risk ratio (RR) = 0.68, P = 0.0007], myocardial infarction (MI, RR = 0.66, P = 0.01), stroke (RR = 0.58, P = 0.003), and BARC major bleeding (RR = 0.63, P = 0.02). There were no significant differences in death from any cause (RR = 1.06, P = 0.59) and vascular death (RR = 0.92, P = 0.62) between the two groups. Conclusions: Patients with CAD use clopidogrel could further reduce the risk of MACCE, MI, stroke, and BARC major bleeding, compared with the use of aspirin. This finding supported the use of clopidogrel rather than aspirin in patients with CAD who required long-term antiplatelet monotherapy for preventing ischemic events.

Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.

SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.

OBJECTIVES: Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism. METHODS: SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. RESULTS: SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ. CONCLUSION: SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.

Potential correlation of oral flora with pemphigus vulgaris - A case control study.

Background/purpose: Oral flora is related to various immune-related diseases. Herein we explored the characteristics of oral flora in patients with pemphigus vulgaris (PV) and analyzed the correlation between oral flora and PV. Materials and methods: Twenty-two untreated patients with PV and 12 healthy controls (HC) were included in this case-control study. The characteristics of salivary microbiome were assessed by high-throughput sequencing using the 16S rRNA Illumina MiSeq approach, and differences between the PV and HC groups were determined. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was applied to screen key metabolic pathways and preliminarily explore potential mechanisms underlying PV occurrence and development. Results: The abundance of oral flora in the PV group was significantly lower than that in the HC group, and there were characteristic changes. The relative abundance of Prevotella and Agrobacterium in the PV group was significantly higher than that in the HC group (P < 0.05) and that of Neisseria, Lautropia, and Fusobacterium was significantly lower (P < 0.05). There was a linear correlation between Prevotella and serum Dsg3 level in PV. KEGG pathway analyses indicated significant differences in nine metabolic pathways between the PV and HC groups (P < 0.05), namely carbohydrate metabolism, digestive system, neurodegenerative disease, glycan biosynthesis and metabolism, drug resistance: antimicrobial, infectious disease: viral, circulatory system, excretory system, and nervous system. Conclusion: The oral flora of patients with PV presented characteristic changes, and several metabolic pathways were affected, including N-glycan biosynthesis and metabolism. Prevotella spp. appear to require the most attention in PV. We believe that oral flora dysbacteriosis contributes to PV occurrence and development.

SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1.

Dysregulation of serine/arginine splicing factors (SRSFs) and abnormal alternative splicing (AS) have been widely implicated in various cancers but scarcely investigated in nasopharyngeal carcinoma (NPC). Here we examine the expression of 12 classical SRSFs between 87 NPC and 10 control samples, revealing a significant upregulation of SRSF3 and its association with worse prognosis in NPC. Functional assays demonstrate that SRSF3 exerts an oncogenic function in NPC progression. Transcriptome analysis reveals 1,934 SRSF3-regulated AS events in genes related to cell cycle and mRNA metabolism. Among these events, we verify the generation of a long isoform of AMOTL1 (AMOTL1-L) through a direct bond of the SRSF3 RRM domain with the exon 12 of AMOTL1 to promote exon inclusion. Functional studies also reveal that AMOTL1-L promotes the proliferation and migration of NPC cells, while AMOTL1-S does not. Furthermore, overexpression of AMOTL1-L, but not -S, significantly rescues the inhibitory effects of SRSF3 knockdown. Additionally, compared with AMOTL1-S, AMOTL1-L has a localization preference in the intracellular than the cell membrane, leading to a more robust interaction with YAP1 to promote nucleus translocation. Our findings identify SRSF3/AMOTL1 as a novel alternative splicing axis with pivotal roles in NPC development, which could serve as promising prognostic biomarkers and therapeutic targets for NPC.

A metabolomics-based analysis of the metabolic pathways associated with the regulation of branched-chain amino acids in rats fed a high-fructose diet.

Previous studies have shown that the elevated levels of circulating branched-chain amino acids (BCAAs) are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyse the metabolic changes associated with high BCAA levels. Sixteen 8-week-old Sprague-Dawley (SD) rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analysed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analysed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.