Shantou Central Hospital

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

AIM: Thalassaemia is a good candidate disease for control by preventive genetic programmes in developing countries. Accurate population frequency data are needed for planning the control of thalassaemia in the high risk Guangdong Province of southern China. METHODS: In total, 13397 consecutive samples from five geographical areas of Guangdong Province were analysed for both haematological and molecular parameters. RESULTS: There was a high prevalence of carriers of alpha thalassaemia (8.53%), beta thalassaemia (2.54%), and both alpha and beta thalassaemia (0.26%). Overall, 11.07% of the population in this area were heterozygous carriers of alpha and beta thalassaemia. The mutation spectrum of alpha and beta thalassaemia and its constitution were fully described in this area. This study reports the true prevalence of silent alpha thalassaemia in the southern China population for the first time. In addition, two novel mutations that give rise to alpha thalassaemia, one deletion resulting in beta thalassaemia, and a rare deletion (--(THAI) allele) previously unreported in mainland China were detected. The frequency of the most common mutation, the Southeast Asian type of deletion (--(SEA), accounting for 48.54% of all alpha thalassaemias) was similar to the total of two alpha(+) thalassaemia deletions (-alpha(3.7) and -alpha(4.2), accounting for 47.49% of alpha thalassaemia). CONCLUSION: Both alpha and beta thalassaemia are widely distributed in Guangdong Province of China. The knowledge gained in this study will enable the projected number of pregnancies at risk to be estimated and a screening strategy for control of thalassaemia to be designed in this area.

Background & AimsLong non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function.MethodsWe studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses.ResultsWe identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling.ConclusionsWe identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients. Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses. We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling. We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients.

Abstract The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1 + myofibroblasts with prognostic values and potential biological significance. CST1 + myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

Interstitial lung disease (ILD) is a major pulmonary manifestation of connective tissue disease (CTD), leading to significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) is presently considered the diagnostic gold standard for pulmonary fibrosis diagnosis and quantification in the clinical arena. However, not negligible doses of ionizing radiation limit the use of HRCT, especially for serial follow-up in younger female patients. In the past decade, lung ultrasound (LUS) has been proposed to assess ILD by detecting and quantifying sonographic B-lines. Previous studies demonstrate that B-lines have a good diagnostic accuracy, especially high sensitivity, and correlate well with HRCT findings, suggesting LUS as a novel, non-invasive, and non-ionizing imaging method to be used in patients with CTD-ILD. Although preliminary data are promising, challenges and controversies still remain. For example, the mechanisms of B-line generation are not fully understood; the diagnostic accuracy and performance characteristics of LUS partially depend on the scanning scheme and scoring system used; and up-to-date B-lines cannot discriminate the early cellular inflammation from the chronic fibrotic phase in CTD-ILD. Therefore it is important for clinicians to understand the strengths and limitations of LUS in CTD-ILD patients, to maximize its value.

Background . Accumulative evidence showed that gut microbiota was important in regulating the development of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablet (HQT), a lipid‐lowering and anti‐inflammatory medicinal formula, has been used to prevent and treat NAFLD. However, its mechanism of action is unknown. The aim of this study was to confirm whether HQT reversed the gut microbiota dysbiosis in NAFLD rats. Methods . We established an NAFLD model of rats fed with a high‐fat diet (HFD), which was given different interventions, and measured the level of liver biochemical indices and inflammatory factors. Liver tissues were stained with hematoxylin‐eosin and oil red O. Changes in the gut microbiota composition were analyzed using 16S rRNA sequencing. Results . The hepatic histology and biochemical data displayed that HQT exhibited protective effects on HFD‐induced rats. Moreover, HQT also reduced the abundance of the Firmicutes / Bacteroidetes ratio in HFD‐fed rats and modified the gut microbial species at the genus level, increasing the abundances of gut microbiota which were reported to have an effect on relieving NAFLD, such as Ruminococcaceae , Bacteroidales_S24-7_group , Bifidobacteria , Alistipes , and Anaeroplasma , and significantly inhibiting the relative abundance of Enterobacteriacea e, Streptococcus , Holdemanella , Allobaculum , and Blautia , which were reported to be potentially related to NAFLD. Spearman’s correlation analysis found that [Ruminococcus]_gauvreauii_group , Lachnoclostridium , Blautia , Allobaculum , and Holdemanella exhibited significant ( p < 0.001) positive correlations with triglyceride, cholesterol, low‐density lipoprotein cholesterol, interleukin‐6, interleukin‐1 β , tumor necrosis factor‐ α , and body weight and negative correlations with high‐density lipoprotein cholesterol ( p < 0.001). The norank_f__Bacteroidales_S24-7_group and Alistipes showed an opposite trend. Moreover, the HQT could promote flavonoid biosynthesis compared with the HFD group. Conclusion . In summary, the HQT has potential applications in the prevention and treatment of NAFLD, which may be closely related to its modulatory effect on the gut microbiota.

Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes-S1 and S2-based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.

Abstract Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD‐1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II‐IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab‐paclitaxel (260 mg/m 2 in total on day 1 and day 8) and cisplatin (75 mg/m 2 in total on days 1‐3) of each 21‐day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2‐year progression‐free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%‐48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%‐70.4%) and treatment‐related adverse events (TRAEs) of low severity (grade 1‐2, 75.0%; grade 3, 10.7%; grade 4‐5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2‐year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long‐term survival analyses.

Background: Accurate identification of pCR to neoadjuvant chemotherapy (NAC) is essential for determining appropriate surgery strategy and guiding resection extent in breast cancer. However, a non-invasive tool to predict pCR accurately is lacking. Our study aims to develop ensemble learning models using longitudinal multiparametric MRI to predict pCR in breast cancer. Methods: From July 2015 to December 2021, we collected pre-NAC and post-NAC multiparametric MRI sequences per patient. We then extracted 14,676 radiomics and 4096 deep learning features and calculated additional delta-value features. In the primary cohort (n = 409), the inter-class correlation coefficient test, U-test, Boruta and the least absolute shrinkage and selection operator regression were used to select the most significant features for each subtype of breast cancer. Five machine learning classifiers were then developed to predict pCR accurately for each subtype. The ensemble learning strategy was used to integrate the single-modality models. The diagnostic performances of models were evaluated in the three external cohorts (n = 343, 170 and 340, respectively). Findings: A total of 1262 patients with breast cancer from four centers were enrolled in this study, and pCR rates were 10.6% (52/491), 54.3% (323/595) and 37.5% (66/176) in HR+/HER2-, HER2+ and TNBC subtype, respectively. Finally, 20, 15 and 13 features were selected to construct the machine learning models in HR+/HER2-, HER2+ and TNBC subtypes, respectively. The multi-Layer Perception (MLP) yields the best diagnostic performances in all subtypes. For the three subtypes, the stacking model integrating pre-, post- and delta-models yielded the highest AUCs of 0.959, 0.974 and 0.958 in the primary cohort, and AUCs of 0.882-0.908, 0.896-0.929 and 0.837-0.901 in the external validation cohorts, respectively. The stacking model had accuracies of 85.0%-88.9%, sensitivities of 80.0%-86.3%, and specificities of 87.4%-91.5% in the external validation cohorts. Interpretation: Our study established a novel tool to predict the responses of breast cancer to NAC and achieve excellent performance. The models could help to determine post-NAC surgery strategy for breast cancer. Funding: This study is supported by grants from the National Natural Science Foundation of China (82171898, 82103093), the Deng Feng project of high-level hospital construction (DFJHBF202109), the Guangdong Basic and Applied Basic Research Foundation (grant number, 2020A1515010346, 2022A1515012277), the Science and Technology Planning Project of Guangzhou City (202002030236), the Beijing Medical Award Foundation (YXJL-2020-0941-0758), and the Beijing Science and Technology Innovation Medical Development Foundation (KC2022-ZZ-0091-5). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

Although hyperandrogenism is an important condition and is considered the possible pathogenesis behind polycystic ovary syndrome (PCOS), data supporting this is still scarce. We sought to determine whether or not prenatal androgen exposure leads to PCOS and the possible cellular mechanisms involved. To induce prenatal androgen exposure, pregnant rats were treated with daily subcutaneous injections of free testosterone (T) or dihydrotestosterone (DHT) from embryonic days 16 to 19, and their female offspring were studied as adults. The mRNA expression of the progesterone receptor (PR) in the preoptic area (POA) hypothalamus was higher in the experimental groups than in the control group after ovariectomy and stimulation with estradiol benzoate. The levels of T, P, leutinizing hormone (LH), and estradiol were higher in the experimental groups than in the control groups. The frequency and magnitude of LH secretion was increased in experimental rats as compared with the control group. The anogenital distance of the experimental groups was prolonged and the nipple number was lower than that of the control group. Almost all experimental rats had prolonged or irregular estrous cycles. The experimental groups had fewer corpus luteum and preovulatory follicles and more preantral follicles and antral follicles than the controls. Our findings are consistent with the hypothesis that excess androgen during the prenatal period may cause PCOS. Additionally, we show that hyperandrogenic interference in the release of preovulatory LH surges is mediated by the suppressive effects of androgens on PR expression in POA-hypothalamic tissue.

Hypertrophic scars (HTS) are caused by dermal injuries such as trauma and burns to the deep dermis, which are red, raised, itchy and painful. They can cause cosmetic disfigurement or contractures if craniofacial areas or mobile region of the skin are affected. Abnormal wound healing with more extracellular matrix deposition than degradation will result in HTS formation. This review will introduce the physiology of wound healing, dermal HTS formation, treatment and difference with keloids in the skin, and it also review the current advance of molecular basis of HTS including the involvement of cytokines, growth factors, and macrophages via chemokine pathway, to bring insights for future prevention and treatment of HTS.

Importance: Schools have been suspended nationwide in 188 countries, and classes have shifted to home-based distance learning models to control the spread of the coronavirus disease 2019 (COVID-19) pandemic. Additional information is needed to determine mental health status among school-aged children and adolescents during this public health crisis and the risk factors associated with psychological distress during the pandemic. Objective: To assess self-reported psychological distress among school-aged children and adolescents associated with the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study using data from a survey on the mental health of school-aged children and adolescents in Guangdong province, China, conducted by using a stratified cluster random sampling method between March 8 to 30, 2020. To estimate outcomes associated with location of districts, only data from students with internet protocol addresses and current addresses in Guangdong were included. Data were analyzed from April 5 to July 20, 2020. Exposure: Home-based distance learning during the COVID-19 pandemic. Main Outcome and Measures: The main outcome was self-reported psychological distress, measured using the total score on the 12-item General Health Questionnaire of 3 or greater. Multivariate logistic regression was used to analyze risk factors associated with mental health status. Odds ratios (ORs) were used to analyze the associations of factors with psychological distress. Results: Among 1 310 600 students who completed the survey, 1 199 320 students (mean [SD] age, 12.04 [3.01] years; 619 144 [51.6%] boys) were included in the final analysis. A total of 126 355 students (10.5%) self-reported psychological distress. Compared with students in primary school, high school students had increased risk of psychological distress (OR, 1.19 [95% CI, 1.15-1.23]). Compared with students who wore a face mask frequently, students who never wore a face mask had increased risk of psychological distress (OR, 2.59 [95% CI, 2.41-2.79]). Additionally, students who spent less than 0.5 hours exercising had increased odds of self-reported psychological distress compared with students who spent more than 1 hour exercising (OR, 1.64 [95% CI, 1.61-1.67]). Conclusions and Relevance: These findings suggest that the prevalence of self-reported psychological distress among students during the COVID-19 pandemic was relatively high. Frequency of wearing a face mask and time spent exercising were factors associated with mental health. Therefore, it may be necessary for governments, schools, and families to pay attention to the mental health of school-aged children and adolescents during the COVID-19 pandemic and take corresponding countermeasures to reduce the impact of the COVID-19 pandemic on students' mental health.

OBJECTIVES: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. METHODS: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student's t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. RESULTS: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1-3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. CONCLUSIONS: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. KEY POINTS: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. METHODS: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. RESULTS: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ = 6.342 and 13.603, P = 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ = 0.016 and 0.382, P = 0.899 and 0.536). CONCLUSION: Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.

Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells' response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer's biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.

Aim: To report the global, regional, and national burden of type 2 diabetes mellitus (T2DM) in 2019, assess its trends in the past, and forecast its trends in the future. Methods: The main data source was the Global Burden of Disease 2019 database. We assessed the changes in T2DM burden from 1990 to 2019 with joinpoint regression analysis. Age-period-cohort analysis was used to forecast the T2DM incidence and mortality rate from 2020 to 2034. Results: The burden of T2DM has increased from 1990 to 2019 generally. The low-middle socio-demographic index (SDI) region had the highest increase in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (ASDR) due to T2DM. Nationally, the increase in ASIR (r=0.151, p=0.046) and the decrease in ASMR (r=0.355, p<0.001) were positively correlated with SDIs. In 2019, the global ASIR, ASPR, ASMR, ASDR due to T2DM were 259.9 (95% UI 240.3-281.4), 5282.9 (95% UI 4853.6-5752.1), 18.5 (95% UI 17.2-19.7), and 801.5 (95% UI 55477000-79005200) per 100,000 population, respectively. Additionally, the ASIR (r=0.153, p=0.030) and ASPR (r=0.159, p=0.024) of T2DM were positively correlated with SDIs, while ASMR (r=-0.226, p=0.001) and ASDR (r=-0.171, p=0.015) due to T2DM were negatively correlated with SDIs. The ASIR was estimated to increase to 284.42, and ASMR was estimated to increase to 19.1 from 2030 to 2034, per 100,000 population. Conclusion: Globally, the burden of T2DM has increased in the past and was forecast to continue increasing. Greater investment in T2DM prevention is needed.

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent causes of cancer death worldwide and effective diagnosis is needed. We assessed the diagnostic potential of an autoantibody panel that may benefit early diagnosis. METHODS: We analyzed data for patients with ESCC and normal controls in a test cohort and a validation cohort. Autoantibody levels were measured against a panel of six tumor-associated antigens (p53, NY-ESO-1, matrix metalloproteinase-7 (MMP-7), heat shock protein 70 (Hsp70), peroxiredoxin VI (Prx VI), and BMI1 polycomb ring finger oncogene (Bmi-1)) by enzyme-linked immunosorbent assay. RESULTS: We assessed serum autoantibodies in 513 participants: 388 with ESCC and 125 normal controls. The validation cohort comprised 371 participants: 237 with ESCC, and 134 normal controls. Autoantibodies to at least 1 of 6 antigens demonstrated a sensitivity/specificity of 57% (95% confidence interval (CI): 52-62%)/95% (95% CI: 89-98%) and 51% (95% CI: 45-57%)/96% (95% CI: 91-99%) in the test and validation cohorts, respectively. Measurement of the autoantibody panel could differentiate early-stage ESCC patients from normal controls (sensitivity 45% (95% CI: 32-59%) and specificity 95% (95% CI: 89-98%) in the test cohort; 46% (95% CI: 35-58%) and 96% (95% CI: 91-99%) in the validation cohort). In either cohort, no significant differences were seen when patients were subdivided by age, gender, smoking status, size of tumor, site of tumor, depth of tumor invasion, histological grade, lymph node status, TNM stage, or early-stage and late-stage groups. CONCLUSIONS: Measurement of an autoantibody response to multiple tumor-associated antigens in an optimized panel assay, to help discriminate early-stage ESCC patients from normal controls, may aid in early detection of ESCC.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. Recently, an elevated NGAL expression was reported in several types of cancers. However, the characteristics of NGAL expression in oesophageal squamous cell carcinoma (ESCC) are still unknown. AIM: To demonstrate the role of NGAL in ESCC. METHODS: NGAL expression in 81 paraffin sections, including ESCC, normal mucosa, simple hyperplasia and dysplasia, and in 73 fresh specimens of ESCC was analysed by immunohistochemistry, western blot and gelatin zymography. RESULTS: On immunohistochemical study, ESCC showed a diverse staining pattern for NGAL. However, only a weak positive signal was present within a restricted cytoplasmic area in the normal oesophageal epithelium. In dysplasia, altered NGAL expression could also be observed. On western blot study, NGAL expression level was found to be significantly higher in ESCC than in normal mucosa (p=0.030), and to be positively correlated with cell differentiation. However, no significant association was observed between NGAL expression and cell proliferation. In addition, the enzymic activity of the NGAL/matrix metalloproteinase 9 complex was much higher in ESCC than in normal mucosa, and was significantly correlated with the depth of tumour invasion in zymography analysis (p=0.006). CONCLUSIONS: The findings suggest that NGAL is involved in the differentiation pathway and invasive progression of ESCC.