Corrigendum: Whole-genome sequencing, annotation, and biological characterization of a novel Siphoviridae phage against multi-drug resistant Propionibacterium acne.

[This corrects the article DOI: 10.3389/fmicb.2022.1065386.].

Development and validation of a nomogram model based on pretreatment ultrasound and contrast-enhanced ultrasound to predict the efficacy of neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer.

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.

Family aggregation and prevalence of other autoimmune diseases in SAPHO syndrome.

Objective: SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a heterogeneous disease that clinically manifests as chronic inflammatory osteoarticular and dermatological lesions. Few reports have described familial clustering of SAPHO syndrome cases. This research aimed to illustrate the family aggregation of SAPHO syndrome and investigate the prevalence of autoimmune disorders among SAPHO syndrome patients and first-degree relatives in a large cohort. Methods: We retrospectively reviewed the medical records of 233 SAPHO patients diagnosed at Peking Union Medical College Hospital. Direct phone calls were made to each first-degree relatives. All relatives of the patients who reported SAPHO syndrome were asked for a detailed outpatient evaluation. Results: A total of 233 patients and 1227 first-degree relatives were recruited. Six (2.6 %) patients had positive SAPHO family history, including four mother-daughter pairs and two sister pairs. Twenty-one (9.0 %) patients presented at least one kind of autoimmune disease, including 12 rheumatoid arthritis and 4 ulcerative colitis cases. Fifty-eight (24.9 %) SAPHO syndrome patients had 68 (5.5 %) first-degree relatives with at least one autoimmune disorder. The palmoplantar pustulosis, psoriasis vulgaris, and rheumatoid arthritis prevalence in our subjects were each higher than reference rates. Conclusion: This is the first evaluation of familial aggregation for SAPHO syndrome in a large cohort. SAPHO syndrome has a weak familial aggregation. There is a relatively high prevalence of coexisting autoimmune disease among patients with SAPHO syndrome and their first-degree relatives. These results would prompt physicians to screen SAPHO syndrome patients and their family members for concomitant autoimmune diseases. Keypoints: This study suggesting a potential genetic component in the pathogenesis of SAPHO syndrome. This study is the first to evaluate the family aggregation of SAPHO syndrome in a large cohort.

Predicting the Efficacy of Neoadjuvant Chemotherapy for Pancreatic Cancer Using Deep Learning of Contrast-Enhanced Ultrasound Videos.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Extracellular Vesicle Content Changes Induced by Melatonin Promote Functional Recovery of Pancreatic Beta Cells in Acute Pancreatitis.

Aim: Acute pancreatitis is an inflammatory disorder of the pancreas, which causes abnormal activation of immune cells. The macrophages were accumulated in pancreas and infiltrated into islets during the AP process to induce abnormal glucose metabolism. However, the role of macrophages in abnormal glucose metabolism remains understood. Extracellular vesicles act in the regulation of intercellular function, but whether EVs secreted by macrophages contribute to ß cell failure and apoptosis in AP is unclear. Based on this, the aim of this study was to reveal the role of macrophages-EVs in AP and develop a treatment for symptoms of hyperglycemia in AP. Methods: The AP model was established and treated by various doses of melatonin to analyze the therapeutic effect. The accumulation and polarization of macrophages in the AP pancreas were observed, and the ß cells were incubated with pancreatic derived EVs to analyze the role in ß cell failure and apoptosis. Results: The results showed that macrophages were recruited and polarized to M1 phenotype macrophages in the pancreas of AP mice, which obtained inflammatory EVs that contained specific miRNAs to induce ß cell failure and apoptosis. Then, the EVs derived from M1 macrophages triggered ß cell failure and apoptosis. Melatonin prevented polarization of macrophages to the M1 phenotype in vivo, which reduced the secretion of inflammatory EVs, changed the abundance of miRNAs in EVs, and therefore decreased inflammatory EV-mediated ß cell failure and apoptosis. Conclusion: Our results demonstrate that similar to 20S proteasome inhibitor MG132, analyses indicated that melatonin prevented degradation of IκBα through the ubiquitylation pathway to restrict p50 subunits to the cytoplasm of macrophages, inhibited activation of the NF-κB pathway to downregulate the transcription of specific miRNAs, and reduced miRNA transport into EVs.

Case report: Peritumoral hepatic steatosis in a patient with a metastatic somatostatin-producing oligosymptomatic neuroendocrine neoplasm.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous collection of tumors derived from various neuroendocrine cells and are divided into functioning NEN and non-functioning NEN. Some NENs present with mild symptoms and can secrete somatostatin. These neoplasms are known as somatostatin-producing oligosymptomatic NENs. In this report, we describe a case of metastatic somatostatin-producing oligosymptomatic NEN with peritumoral hepatic steatosis and review the relevant literature. The patient was a 45-year-old woman who presented with mild steatorrhea and melena. A computed tomography scan revealed an enlarged pancreas protruding into the duodenum. Pathology after total pancreatectomy showed a grade 2 pancreatic NEN with positive somatostatin immunostaining. Enlarging masses on the liver were observed after the operation. Ultrasound examination revealed several lesions in the liver, with inner hypoechoic areas that showed rapid enhancement and fast washout on contrast-enhanced ultrasonography and with outer hyperechoic areas with continuous iso-enhancement. Therefore, the inner hypoechoic areas seen on contrast-enhanced ultrasonography were suspected to be true metastases. A biopsy confirmed this suspicion and indicated that the outer areas were peritumoral liver steatosis. This case highlights the importance of the imaging pattern described in this report for accurate diagnosis of metastatic NEN to avoid incorrect estimation of tumor size or a missed diagnosis on biopsy.

Whole-genome sequencing, annotation, and biological characterization of a novel Siphoviridae phage against multi-drug resistant Propionibacterium acne.

Antibiotics-resistant Propionibacterium acne (P. acne) causes severe acne vulgaris, serious public health, and psychological threat. A new lytic bacteriophage (phage), φPaP11-13, infecting P. acne, was isolated from the sewage management center of Xinqiao Hospital. It can form transparent plaque with diameters of 1.0 ~ 5.0 mm on the double-layer agar plate, indicating a robust lytic ability against its host. Transmission electron microscopy (TEM) showed that φPaP11-13 belonged to the Siphoviridae family (head diameter 60 ± 4.5 nm, tail length 170 ± 6.4 nm, tail width 14 ± 2.4 nm). The one-step growth curve showed the incubation period was 5 h, and the burst size was 26 PFU (plaque-forming unit)/cell. Moreover, it exhibited tolerance over a broad range of pH and temperature ranges but was utterly inactivated by ultraviolet (UV) irradiation for 1 h. The whole-genome sequencing results revealed φPaP11-13 had a linear dsDNA with 29,648 bp length. The G/C content was 54.08%. Non-coding RNA genes and virulence factors were not found. Forty five open reading frames (ORFs) were identified after online annotation. This study reports a novel P. acne phage φPaP11-13, which has a robust lytic ability, no virulence factors, and good stability. The characterization and genomic analysis of φPaP11-13 will develop our understanding of phage biology and diversity and provide a potential arsenal for controlling antibiotics-resistant P. acne-induced severe acne vulgaris.

The Effect of 3D Printing Metal Materials on Osteoporosis Treatment.

3D printing has been in use for a long time and has continued to contribute to breakthroughs in the fields of clinical, physical, and rehabilitation medicine. In order to evaluate the role of 3D printing technology in treating spinal disorders, this paper presents a systematic review of the relevant literature. 3D printing is described in terms of its adjunctive function in various stages of spinal surgery and assistance in osteoporosis treatment. A review of metal 3D printed materials and applications of the technology is also provided.

Non-Hermitian effective medium theory and complex Dirac-like cones.

In this work, we propose a non-Hermitian effective medium theory to interpret the spawning rings of exceptional points out of the Dirac cones in the band structures of photonic crystals with loss/gain. Based on this theory, we predict and demonstrate two unique types of band dispersions of fully passive photonic crystals. In one type, the exceptional ring shrinks into a complex Dirac point associated with a complex Dirac-like cone. In the other type, a point of quadratic degeneracy is realized in the imaginary frequency spectrum. Our theory provides a unified picture for the exceptional points in effective media and gives rise to novel concepts like complex Dirac-like cones in non-Hermitian photonics.

Development and Application of Artificial Intelligence in Auxiliary TCM Diagnosis.

As an emerging comprehensive discipline, artificial intelligence (AI) has been widely applied in various fields, including traditional Chinese medicine (TCM), a treasure of the Chinese nation. Realizing the organic combination of AI and TCM can promote the inheritance and development of TCM. The paper summarizes the development and application of AI in auxiliary TCM diagnosis, analyzes the bottleneck of artificial intelligence in the field of auxiliary TCM diagnosis at present, and proposes a possible future direction of its development.

Clinical characteristics of pediatric synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: the first Chinese case series from a single center.

INTRODUCTION: Pediatric SAPHO syndrome is regarded as the equivalent of chronic recurrent multifocal osteomyelitis or chronic non-bacterial osteomyelitis. This study aimed to evaluate the clinical features and treatment options for Chinese pediatric patients with SAPHO syndrome. METHOD: We conducted a single-center, retrospective study on a sample of 24 pediatric patients with SAPHO syndrome who were diagnosed at Peking Union Medical College Hospital from April 2014 to August 2018. The demographic, clinical, laboratory, imaging, histological, and therapeutic data were collected and analyzed. RESULTS: A total of 15 boys and 9 girls were included. The mean age of onset of bone and skin symptoms was 11.7 ± 3.8 and 14.4 ± 2.7 years, respectively. The mean follow-up period was 39.2 months. Seventeen patients had skin manifestations (46% had severe acne, 100% were boys; 21% had palmoplantar pustulosis, 100% were girls). Bone lesions were localized in four of the following major regions: anterior chest wall (42%), mandible (29%), peripheral bones (50%), and spine and sacroiliac joints (21%). Six patients had been treated with non-steroidal anti-inflammatory drugs, 10 with bisphosphonate, 10 with a tumor necrosis factor-α antagonist, and 1 with glucocorticoids, with variable responses. A total of 70% of the patients had complete remission after bisphosphonate or TNF-α antagonist therapy. CONCLUSION: Pediatric patients with SAPHO syndrome have different characteristics from other cohorts in the sex ratio, frequency of mandibular involvement, and sex distribution of skin lesions. Bisphosphonate and TNF-α antagonists show a favorable response in pediatric SAPHO syndrome treatment. Key points •Being the first study that describes an Asian pediatric SAPHO case series. •Chinese pediatric patients with SAPHO syndrome have different characteristics from Chinese adult patients and Caucasian pediatric patients.

Clinical features of a Chinese female nongestational choriocarcinoma cohort: a retrospective study of 37 patients.

BACKGROUND: Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease. RESULTS: We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively. CONCLUSIONS: Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.

Characteristics of adult abdominal cystic Lymphangioma: a single-center Chinese cohort of 12 cases.

BACKGROUND: Cystic lymphangioma is a rare, benign developmental disease, mostly affecting the cervical and axial regions. The clinical features of abdominal cystic lymphangioma (ACL) are reported among pediatric patients but are less well known in adults. The purpose of this study was to demonstrate the clinical characteristics of ACL in Chinese adults and describe our experience in treating this disease. METHODS: We conducted a single-center, non-interventional, retrospective study of 12 adult patients with ACL admitted to Peking Union Medical College Hospital in Beijing, China from November 1984 through August 2017. The demographic, clinical, laboratory, imaging, histopathologic, and therapeutic data were collected. RESULTS: Detailed information on seven males and five females was available. The mean age at diagnosis was 39.1 (SD 17.3) years. The mean duration of follow-up was 6.9 years. Six (50%) patients were asymptomatic, and abdominal pain was the leading symptom for three (25%) patients. The cysts were evaluated by ultrasound (n = 8, 67%), CT (n = 10, 83%), and MRI (n = 4, 33%). Therapeutic modalities include laparotomy (n = 6, 50%), laparoscopy (n = 4, 33%), and aspiration (n = 2, 17%), with variable outcomes. The mean postsurgical hospital stay was 6.8 days. Complete excision was accomplished in eight patients, and one recurrence was observed during follow-up. Of patients who underwent partial resection, one experienced disease relapse. CONCLUSIONS: This is the first report on an Asian cohort of adult patients with ACL. Typical imaging features could lead to timely diagnosis and treatment of ACL. Radical resection is recommended with a longer period of follow-up. The analysis of this cohort deepens our understanding of adult ACL.

Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation­induced apoptosis in brain by increasing autophagy involved in AdipoR1­AMPK signaling.

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia­reperfusion (GCIR)­induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest­cardiopulmonary resuscitation (CA­CPR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal death in GCIR­injured brain post­CA­CPR. Using normal controls (Sham group) and two experimental groups [CA­CPR­induced GCIR injury (PCAS) group and exogenous treatment with adiponectin post­CA­CPR (APN group)], it was demonstrated that both apoptosis and autophagy were observed simultaneously in the brain subjected to GCIR, but apoptosis appeared to be more apparent. Exogenous administration of APN significantly reduced the formation of malondialdehyde, a marker of oxidative stress and increased the expression of superoxide dismutase, an anti­oxidative enzyme, resulting in the stimulation of autophagy, inhibition of apoptosis and reduced brain tissue injury (P<0.05 vs. PCAS). APN treatment increased the expression of APN receptor 1 (AdipR1) and the phosphorylation of AMP­activated protein kinase (AMPK; Ser182) in brain tissues. In conclusion, GCIR induced apoptosis and inhibited autophagy, contributing to brain injury in CA­CPR. By contrast, APN reduced the brain injury by reversing the changes of neuronal autophagy and apoptosis induced by GCIR. The possible mechanism might owe to its effects on the activation of AMPK after combining with AdipR1 on neurons, which suggests a novel intervention against GCIR injury in CA­CPR conditions.