Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study.

BACKGROUND: Previous studies have demonstrated the benefits of ideal cardiovascular health (CVH) in reducing cardiovascular risk. However, its role in subclinical atherosclerosis (SA) progression remains unclear. We aim to examine the association of CVH, estimated by the American Heart Association's new Life's Essential 8 (LE8), with the progression of SA. METHODS: This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for 5.7 years. The LE8 score (range, 0-100) consisted of blood pressure, lipids, glucose, body mass index, smoking status, diet health, physical activity and sleep health was evaluated in 1998 and 2008-2009. Progression of SA was determined by carotid plaque and coronary artery calcification (CAC) in 2008-2009 and 2013-2014. Log-binomial regression model was used to estimate the association of LE8 score with SA progression. RESULTS: Each 10 points increment in LE8 score was associated with 15.2% (RR: 0.848, 95% CI: 0.797-0.902), 17.7% (RR: 0.823, 95% CI: 0.766-0.884) and 12.0% (RR: 0.880, 95% CI: 0.845-0.916) lower risks of carotid plaque, CAC and overall SA progression, respectively. Compared with participants with non-ideal CVH at both visits, the participants with ideal CVH at both visits had 39.1% (RR: 0.609, 95% CI: 0.494-0.752), 41.0% (RR: 0.590, 95% CI: 0.456-0.764) and 29.7% (RR: 0.703, 95% CI: 0.598-0.825) lower risks of carotid plaque, CAC and overall SA progression, respectively. CONCLUSIONS: Higher LE8 scores were associated with lower risks of SA progression. Besides, long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

Gut microbiota modulating intestinal stem cell differentiation.

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

Research progress in the treatment of schistosomiasis with traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. AIM OF THE STUDY: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. MATERIALS AND METHODS: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. RESULTS: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. CONCLUSION: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.

Probing cell metabolism using the two-photon excitation autofluorescence lifetime of tryptophan.

Compared to intensity detection, fluorescence lifetime has the advantage of being unaffected by variations in excitation intensity, fluorophore concentration, or attenuation due to biological absorption and scattering. In this Letter, to the best of our knowledge, we present the use of the two-photon excitation autofluorescence lifetime imaging of tryptophan (TRP) to probe cell metabolism for the first time. Tests of pure chemical samples showed that the fluorescence lifetime of TRP was highly sensitive to changes in molecular conformation and the environment. In in vitro cell experiments, we successfully utilized the fluorescence lifetime of TRP to distinguish tumor cells from healthy cells, track the therapeutic effect of the tumor immunotherapy drug 1-MT for HeLa cells, and monitor cells in response to carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced cell apoptosis. These results reveal that the two-photon excitation autofluorescence lifetime of TRP could be a sensitive natural probe of cell metabolism in living cells.

Comparison of midterm efficacy of Kirschner wires and elastic intramedullary nails after closed reduction of Judet type 3 radial neck fractures in children: a multicenter study.

Objective: The objective of this study was to compare the midterm efficacy of Kirschner wires and elastic intramedullary nails after the closed reduction treatment of Judet 3 radial neck fractures in children. Methods: This was a retrospective multicenter study of patients diagnosed with Judet type 3 radial neck fractures who underwent closed reduction and internal fixation at four tertiary hospitals from January 2019 to December 2021. Gender, age, fracture type, operation time, follow-up time, x-ray results and complications were collected. The recovery of elbow joint between the two internal fixation methods, elbow motion and complications at the last follow-up were compared. Results: The average operation time of EIN group was statistical significantly increased compared with KW group. There were no significant differences in MEPS score and ROM 3 months after surgery between the two groups, but the ROR Angle of EIN group was statistical significantly increased compared with KW group 3 months after surgery. There were no significant differences in MEPS score, ROM and ROR at the last follow-up. The incidence of complications in EIN group was significantly lower than that in KW group. Conclusion: The use of elastic intramedullary nails fixation or Kirschner wires fixation in the treatment of radial neck fractures in children can both achieve satisfactory fracture reduction and healing. Compared with elastic intramedullary nails, the operation time of Kirschner wires fixation is shorter, and the internal fixation does not need to be removed under anesthesia again, but the complication rate is higher.

Recent advance of ATP citrate lyase inhibitors for the treatment of cancer and related diseases.

ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.

Outcomes of Robotic Versus Laparoscopic Pancreatoduodenectomy Following Learning Curves of Surgeons: A Multicenter Study on 2255 Patients.

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Quantitative multiphoton imaging of cell metabolism, stromal fibers, and keratinization enables label-free discrimination of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) features atypical clinical manifestations and a low 5-year survival rate (< 5% in many developing countries where most of the disease occurs). Precise ESCC detection and grading toward timely and effective intervention are therefore crucial. In this study, we propose a multidimensional, slicing-free, and label-free histopathological evaluation method based on multispectral multiphoton fluorescence lifetime imaging microscopy (MM-FLIM) for precise ESCC identification. To assess the feasibility of this method, comparative imaging on fresh human biopsy specimens of different ESCC grades is performed. By constructing fluorescence spectrum- and lifetime-coded images, ESCC-induced morphological variations are unveiled. Further quantification of cell metabolism and stromal fibers reveals potential indicators for ESCC detection and grading. The specific identification of keratin pearls provides additional support for the early detection of ESCC. These findings demonstrate the viability of using MM-FLIM and the series of derived indicators for histopathological evaluation of ESCC. As there is an increasing interest in developing multiphoton endoscopes and multiphoton FLIM systems for clinical use, the proposed method would probably allow noninvasive, label-free, and multidimensional histological detection and grading of ESCC in the future.

Anesthesia for extracorporeal membrane oxygenation-assisted thoracoscopic lower lobe subsegmental resection in a patient with a single left lung: A case report.

BACKGROUND: It is difficult and risky for patients with a single lung to undergo thoracoscopic segmental pneumonectomy, and previous reports of related cases are rare. We introduce anesthesia for Extracorporeal membrane oxygenation (ECMO)-assisted thoracoscopic lower lobe subsegmental resection in a patient with a single left lung. CASE SUMMARY: The patient underwent comprehensive treatment for synovial sarcoma of the right lung and nodules in the lower lobe of the left lung. Examination showed pulmonary function that had severe restrictive ventilation disorder, forced expiratory volume in 1 second of 0.72 L (27.8%), forced vital capacity of 1.0 L (33%), and maximal voluntary ventilation of 33.9 L (35.5%). Lung computed tomography showed a nodular shadow in the lower lobe of the left lung, and lung metastasis was considered. After multidisciplinary consultation and adequate preoperative preparation, thoracoscopic left lower lung lobe S9bii+S10bii combined subsegmental resection was performed with the assistance of total intravenous anesthesia and ECMO intraoperative pulmonary protective ventilation. The patient received postoperative ICU supportive care. After surgical treatment, the patient was successfully withdrawn from ECMO on postoperative Day 1. The tracheal tube was removed on postoperative Day 4, and she was discharged from the hospital on postoperative Day 15. CONCLUSION: The multi-disciplinary treatment provided maximum medical optimization for surgical anesthesia and veno-venous ECMO which provided adequate protection for the patient's perioperative treatment.

AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway.

Background: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare folate-modified liposomes loaded with resveratrol to investigate its anti-osteosarcoma effect in vitro and in vivo. Methods: We prepared and characterized resveratrol liposomes modified with folate (denoted as, FA-Res/Lps). The effects of FA-Res/Lps on human osteosarcoma cell 143B proliferation, apoptosis, and migration were investigated by MTT, cell cloning, wound-healing assay, transwell, and flow cytometry. A xenograft tumor and lung metastasis model of osteosarcoma was constructed to study the therapeutic effects of FA-Res/Lps on the growth and metastasis of osteosarcoma in vivo. Results: The FA-Res/Lps were prepared with a particle size of 118.5 ± 0.71 and a small dispersion coefficient of 0.154 ± 0.005. We found that FA-modified liposomes significantly increased resveratrol uptake by osteosarcoma cells 143B in flow cytometric assay, resulting in FA-Res/Lps, which inhibit tumor proliferation, migration and induce apoptosis more effectively than free Res and Res/Lps. The mechanism of action may be associated with the inhibition of JAK2/STAT3 signaling. In vivo imaging demonstrated that FA-modified DiR-modified liposomes significantly increased the distribution of drugs at the tumor site, leading to significant inhibition of osteosarcoma growth and metastasis by FA-Res/Lps. Furthermore, we found that FA-Res/Lps did not cause any adverse effects on mice body weight, liver, or kidney tissues. Conclusion: Taken together, the anti-osteosarcoma effect of resveratrol is significantly enhanced when it is loaded into FA-modified liposomes. FA-Res/Lps is a promising strategy for the treatment of osteosarcoma.

[Chemerin mediated neutrophil infiltration in oral squamous cell carcinoma and predicted poor prognosis].

PURPOSE: To explore the effect of Chemerin in oral squamous cell carcinoma (OSCC) tissue on neutrophils infiltration and its possible molecular mechanism. METHODS: The relationship between Chemerin expression and neutrophils density was assessed via double immunohistochemistry staining.The chemotactic effect of Chemerin on neutrophils in OSCC was detected by transwell assay, real-time quantitative PCR(qRT-PCR), Western blot, enzyme-linked immunosorbent assay(ELISA) and flow cytometry. The data were statistically analyzed using SPSS 23.0 software package. The relationship between Chemerin expression and neutrophils density was assessed using Spearman rank correlation analysis. ChemR23 knockout efficiency and chemotactic index were calculated by ANOVA. The relationship between Chemerin expression, neutrophils density and clinicopathological factors was analyzed by Mann-Whitney test. Kaplan-Meier test and Log rank test were used for survival analysis, and risk factors affecting the survival of OSCC patients was assessed using Cox regression model. RESULTS: Double immunohistochemistry staining showed that overexpression of Chemerin was significantly correlated with increased neutrophils infiltration in OSCC(P=0.023), and strong Chemerin expression and high neutrophils density were associated with higher clinical stage(P＜0.001), cervical lymph node metastasis (P＜0.001) and tumor recurrence (P=0.002). Kaplan-Meier survival analysis showed that patients in the strong Chemerin expression + high neutrophils density group had shortened cancer-related overall survival time and disease-free survival time compared with the other two groups. Transwell assay results showed that both OSCC cells and R-Chemerin had a significant chemotactic effect on dHL-60 cells; knockdown of ChemR23 suppressed Chemerin-induced chemotaxis to dHL-60 cells. CONCLUSIONS: Overexpression of Chemerin in OSCC tissue chemoattracts more neutrophils to tumor sites through its receptor ChemR23 and is related to poor clinical prognosis.

Gambogic acid affects high glucose-induced apoptosis and inflammation of retinal endothelial cells through the NOX4/NLRP3 pathway.

Background: This study aimed to investigate the effect and mechanism of gambogic acid (GA) on the apoptosis and inflammation of human retinal endothelial cells (HRECs) under high glucose conditions. Methods: HRECs were cultured in a high glucose medium to simulate retinal endothelial cell injury induced by diabetic retinopathy. Flow cytometry was used to analyze the apoptosis level of HRECs. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Western blotting was applied to detect the intracellular apoptosis-related proteins and expression levels of NADPH oxidase 4 (NOX4), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin (IL)-1ß. Enzyme linked immunosorbent assay (ELISA) was utilized to detect the expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) in the cell supernatants. The messenger RNA (mRNA) levels of IL-6, IL-8, IL-10, and TNF-α were detected by reverse transcription-polymerase chain reaction (RT-qPCR). Results: We observed that high glucose induced the apoptosis and inflammation of HRECs. In addition, the high glucose environment promoted NOX/NLRP3 pathway activation. The activity of HRECs was not significantly affected by the presence of 20 µM or less of GA, and 15 µM of GA could restore the diminished activity of HRECs induced by high glucose. The apoptosis of HRECs cultured under high glucose conditions was significantly inhibited (P<0.05), the levels of IL-6, IL-8, and TNF-α in the cell supernatant were significantly decreased (P<0.05), and the levels of IL-10 were significantly increased (P<0.05). Meanwhile, the relative mRNA expression levels of IL-6, IL-8, and TNF-α in HRECs were significantly decreased (P<0.05), while those of IL-10 were significantly increased (P<0.05). The activity of the high glucose-induced NOX4/NLRP3 pathway in HRECs was significantly inhibited after treatment with 15 µM of GA (P<0.05). Following activation of the NOX4/NLRP3 pathway in HRECs, the apoptosis level was significantly increased (P<0.05), and the inflammatory response was aggravated (P<0.05). Inhibiting the activity of the intracellular NOX4/NLRP3 pathway markedly inhibited cell apoptosis and the inflammatory response (P<0.05). Conclusions: GA can inhibit the apoptosis and inflammation of HRECs under high glucose conditions by inhibiting the activity of the NOX4/NLRP3 pathway. This has a significant inhibitory effect on diabetic retinopathy, which is worthy of further study.

Efficacy Evaluation of Bevacizumab Combined with Capecitabine in the Treatment of HER2-Negative Metastatic Breast Cancer: A Meta-Analysis.

Objective: This study aims to evaluate the efficacy of bevacizumab combined with capecitabine in treating HER2-negative metastatic breast cancer through meta-analysis. Methods: We searched literature from databases, including PubMed, Web of Science, Wiley Online Library, Ovid, CNKI, and Wanfang databases, for randomized controlled trials (RCTs) of bevacizumab combined with capecitabine (experimental group) and other treatments (control group) for HER2-negative metastatic breast cancer. Retrieved articles were published from the establishment of the database to August 9, 2022. The main outcome indicators were disease progression rate (RDP), disease progression-free survival (PFS), 1-year survival rate (OSR), the occurrence of serious adverse events (SAEs), and objective remission rate (ORR). The risk of bias was assessed according to the Cochrane systematic evaluation tool. Then, the meta-analysis was carried out using Stata16.0 software, and subgroup analysis was carried out based on various intervention methods in the control group. Results: 8 RCTs were finally included in this study, including 2470 patients with HER2-negative metastatic breast cancer. The results of meta-analysis showed that bevacizumab combined with capecitabine had no significant advantage over the control group in terms of RDP, but the results of subgroup analysis were consistent and significant (subgroup 1 (bevacizumab or chemotherapy): DR = -0.03, 95% CI (-0.14, 0.09), P = 0.01; subgroup 2 (bevacizumab plus paclitaxel therapy): DR = -0.03, 95% CI (-0.14, 0.09), P = 0.03). Furthermore, there was no statistical difference in terms of PFS of the experimental group (MD = 9.24, 95% CI (7.88, 32.67), P = 0.05). However, the subgroup analysis showed that the combination of bevacizumab and capecitabine demonstrated a more significant significance than bevacizumab or chemotherapy alone (subgroup 1: MD = 10.11, 95% CI (7.88, 12.34), P = 0.00). Compared with the control group, the experimental group had significant differences in OSR (DR = 0.07, 95% CI (-0.01, 0.15), P = 0.00) and ORR (DR = 0.07, 95% CI (-0.01, 0.15), P = 0.00). In terms of safety, the incidence of serious adverse events in the experimental group did not show a statistically significant difference (MD = 0.01, 95% CI (-0.21, 0.19), P = 0.82). When subgroup analyses were performed, the bevacizumab plus capecitabine regimen was associated with an increased incidence of serious adverse events compared with the drug alone (subgroup 1: MD = 0.02, 95% CI (-0.16, 0.20), P = 0.00) but a reduction in serious adverse events compared with the bevacizumab plus paclitaxel regimen (subgroup 2: DR = -0.01, 95% CI (-0.21, 0.19), P = 0.00). Conclusion: The combination therapy of bevacizumab and capecitabine can significantly improve the RDP and OSR of patients compared with the control group. The PFS and ORR of the experimental group are significantly higher than those of bevacizumab or chemotherapy alone. Still, no statistical difference was observed for these outcome indicators between two combined treatments of bevacizumab with capecitabine or paclitaxel. Although this combined treatment scheme may increase the incidence of serious adverse events compared with that of bevacizumab or chemotherapy alone, the incidence of adverse events was decreased compared with bevacizumab combined with paclitaxel. Therefore, the chemotherapy regimen for HER2-negative metastatic breast cancer in clinical practice can be selected according to the actual situation of the patients.

Rapid and label-free histological imaging of unprocessed surgical tissues via dark-field reflectance ultraviolet microscopy.

Routine examination for intraoperative histopathologic assessment is lengthy and laborious. Here, we present the dark-field reflectance ultraviolet microscopy (DRUM) that enables label-free imaging of unprocessed and thick tissues with subcellular resolution and a high signal-to-background ratio. To the best of our knowledge, DRUM provides image results for pathological assessment with the shortest turnaround time (2-3 min in total from sample preparation to tissue imaging). We also proposed a virtual staining process to convert DRUM images into pseudo-colorized images and enhance the image familiarity of pathologists. By imaging various tissues, we found DRUM can resolve cell nuclei and some extranuclear features, which are comparable to standard H&E images. Furthermore, the essential diagnostic features of intraoperatively excised tumor tissues also can be revealed by DRUM, demonstrating its potential as an additional aid for intraoperative histopathology.

Corticosteroids in patients undergoing cardiac surgery: A meta-analysis of 12,559 patients.

OBJECTIVE: Corticosteroids can attenuate the inflammatory response to cardiopulmonary bypass, but their benefits on clinical outcomes are unclear. We conducted a meta-analysis to evaluate whether corticosteroid therapy affects outcomes in patients undergoing cardiac surgery. METHODS: We searched PubMed, Embase, EBSCO and Cochrane databases from 1 January 2010 to 14 March 2022 for randomized controlled trials (RCTs) that assessed corticosteroid versus non- corticosteroid therapy in patients undergoing cardiac surgery. The primary outcome was in-hospital mortality. Secondary outcomes were renal failure, infection, delirium, intensive care unit (ICU) and hospital stay. RESULTS: Four RCTs including 12,559 patients (6265 randomized to corticosteroid therapy and 6294 to non-corticosteroid therapy) were included. One-hundred and 92 of 6265 patients (3.1%) randomized to the corticosteroid group versus 221 of 6294 patients (3.5%) randomized to the non-corticosteroid group experienced death during hospitalization. Compared the control group, corticosteroid therapy did not significantly reduce in-hospital mortality, with an RR of 0.87 (0.72-1.06), p = .16. There was no difference in the incidence of infection (RR 0.78 (0.56-1.10), p = .16), delirium during hospitalization (RR 1.01 (0.90-1.14), p = .85), or the length of hospital stay (MD -0.13 (-0.32 to 0.05), p = .17). However, corticosteroid therapy significantly reduced the risk of renal failure ( RR 0.82 (0.67-0.99), p = .04), and the length of ICU stay (MD -0.41 (-0.65 to -0.17), p < .01). CONCLUSIONS: Corticosteroids did not significantly reduce the rates of in-hospital mortality, infection, or delirium, but reduce the incidence of renal failure and the length of ICU stay.

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Ticagrelor for patients undergoing coronary artery bypass grafting: A meta-analysis of randomized controlled trials.

OBJECTIVE: Ticagrelor may be an alternative to aspirin as it provides robust and consistent platelet inhibition. However, the effect of ticagrelor treatment in patients undergoing coronary artery bypass grafting (CABG) has not been well confirmed. We conducted a meta-analysis to appraise whether ticagrelor therapy affects outcomes in CABG patients. METHODS: We searched PubMed, Embase, EBSCO, and Cochrane databases from its inception up to 4 December 2020 for randomized controlled trials that assessed ticagrelor versus non-ticagrelor in patients undergoing CABG. The primary outcome was the incidence of saphenous vein graft (SVG) occlusion at 1 year after CABG. Secondary outcomes were SVG occlusion at 7 days, major adverse cardiovascular events (MACE), and bleeding requiring reoperation. RESULTS: Seven trials including 4305 patients (2153 randomized to ticagrelor therapy and 2152 to non-ticagrelor therapy) were included. One-hundred and thirty of 1140 patients (11.4%) randomized to the ticagrelor group versus 175 of 1220 patients (14.3%) randomized to the non-ticagrelor group experienced SVG occlusion at 1 year after CABG. Compared to the control group, ticagrelor therapy yielded a significantly lower risk of SVG occlusion [RR 0.79 (0.64-0.97), p = 0.03]. In the subgroup analysis, ticagrelor plus aspirin compared with aspirin alone did not decrease the risk of SVG occlusion after 1 year [RR 0.65 (0.40-1.07), p = 0.09]. There was no difference in the incidence of SVG occlusion at 7 days [RR 0.67 (0.42-1.06), p = 0.09], MACE up to 1 year [RR 0.99 (0.81-1.21), p = 0.90], or bleeding requiring reoperation [RR 1.16 (0.80-1.70), p = 0.44]. CONCLUSIONS: Compared with non-ticagrelor therapy, ticagrelor decreased the risk of saphenous vein graft occlusion after 1 year in patients undergoing elective CABG with saphenous vein grafting.

Follow-up study on ThinPrep cytology test-positive patients in tropical regions.

BACKGROUND: As shown in the statistics from the World Health Organization, it is estimated that approximately 75000 new cases of cervical cancer occur every year in China. In 2008, 33000 people died of cervical cancer in China. It is proven that most women are at risk of cervical cancer. The progression from human papillomavirus (HPV) infection to cervical cancer can be several years or decades, which offers a unique opportunity to prevent cancer. AIM: To observe the changes in ThinPrep cytology tests (TCT) and HPV infection in patients who were detected to be positive via TCT screening of cervical cancer and further explore the biopsy results. METHODS: This paper performed a follow-up study on 206 cervical cancer screening-positive patients of 12231 total cases from our previous research. We conducted an observational study on the TCT results based on the interpretation of The Bethesda System. RESULTS: Over a 5-year period, 10 cases received consistent follow-up. The proportions of cases in which glandular epithelial lesions were detected increased over the follow-up period. The differences between the years were statistically significant (P < 0.01). Over the 5 years, the proportion of patients whose squamous epithelial lesions transformed into glandular epithelial lesions increased yearly. Annual positive rates of HPV infection were: year 1, 73% (24/33); year 2, 43% (6/14); year 3, 36% (9/25); year 4, 50% (9/18); and year 5, 25% (6/24). The positive detection rate after biopsy over a 9-year period was 29%. CONCLUSION: The follow-up study for 5 years to 9 years revealed a tendency to change from squamous epithelial lesions to glandular epithelial lesions and an improvement of the disease (which had not been reported previously). The HPV test indicated a high negative conversion ratio of the viral infection. However, the follow-up cases were not found to have persistent infection of high-risk HPV. Therefore, early intervention of cervical cancer screening is necessary. Low re-examination compliance, patient education, and preventive measures should be enhanced.