Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.
Carbohydrates ; Glycosides ; Oligosaccharides ; Oxidation-Reduction ; Polysaccharides/chemistry*

OBJECTIVE: To investigate the expression of programmed death receptor-1 (PD-1) and inducible costimulator (ICOS) on the surface of CD8⁺ T cells in peripheral blood of patients with primary immune thrombocytopenia (ITP), and explore the roles of PD-1 and ICOS in the occurrence and development of ITP. METHODS: A total of 28 ITP patients treated in Tianjin Medical University General Hospital from September to December 2020 were selected, including 13 patients with newly diagnosed ITP, 15 patients with chronic ITP, and 22 healthy volunteers were recruited as control group. Flow cytometry was used to detect the expression levels of PD-1 and ICOS, and evaluate their correlation with clinical indicators. RESULTS: The percentage of CD8 ⁺ T cells in ITP patients of chronic group was higher than that of the newly diagnosed group and the control group (P<0.05). The expression level of PD-1 on CD8⁺ T cells in ITP patients of newly diagnosed group and chronic group were significantly lower than that of the control group (P<0.05), while the expression level of ICOS were significantly higher (P<0.05). In ITP patients, PD-1 was negatively correlated with platelet count (r=-0.4942, P<0.01), but positively with ICOS (r=0.4342). PD-1 and ICOS were both negatively correlated with lymphocyte count (r_PD-1=-0.4374; r_ICOS=-0.4492). CONCLUSION In ITP patients, the unbalanced expression of PD-1 and ICOS may interfere with the immune homeostasis of the body, which can be used as a therapeutic target for ITP patients.
CD8-Positive T-Lymphocytes/metabolism* ; Flow Cytometry ; Humans ; Inducible T-Cell Co-Stimulator Protein/metabolism* ; Platelet Count ; Programmed Cell Death 1 Receptor/metabolism* ; Purpura, Thrombocytopenic, Idiopathic

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.
Bacterial Infections ; Humans ; Polysaccharides/chemistry* ; Structure-Activity Relationship

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

D-Glycero-D-mannno-heptose 1β, 7-bisphosphate (HBPβ) is an important intermediate for constructing the core structure of Gram-negative bacterial lipopolysaccharides and was reported as a pathogen-associated molecular pattern (PAMP) that regulates immune responses. HBPβ with 3-O-amyl amine linker and its monophosphate derivative D-glycero-D-mannno-heptose 7-phosphate (HP) with 1α-amyl amine linker have been synthesized as candidates for immunity study of HBPβ. The O3-amyl amine linker of heptose was installed by dibutyltin oxide-mediated regioselective alkylation under fine-tuned protecting condition. The stereoselective installation of 1β-phosphate ester was achieved by NIS-mediated phosphorylation at low temperature. The strategy for installation of 3-O-amyl amine linker onto HBP derivative can be expanded to the syntheses of other conjugation-ready carbohydrates bearing anomeric phosphoester.

Since the outbreak of corona virus disease-2019 (COVID-19), the timely intervention of Chinese medicine has played an important role， it can significantly improve the clinical symptoms of patients, alleviate fever, cough, shorten the course of disease and reduce the conversion rate of mild disease to severe disease， moreover, it has obvious advantages in improving survival rate, prognosis and quality of life in patients. In order to make better use of the therapeutic effect of Chinese medicine and overcome the epidemic situation as soon as possible, various provinces, municipalities and autonomous regions have introduced local Chinese medicine treatment schemes in accordance with the geography, climate and epidemic situation. In this article, we have analyzed the similarities and differences among treatment schemes from the perspective of three factors, and it is believed that the onset season is the same for this disease, and the differences between treatment schemes mainly depend on geographical and climatic factors. The results showed that in seven regions of China, the early symptoms in warm and humid regions such as Central China, South China, East China and Southwest China were characterized by "wet, warm, hot, and toxic", and treatment schemes mainly adopted the recipes with clearing heat and detoxifying, strengthening spleen and removing dampness functions. The early symptoms in cold regions such as Northeast China, North China, and Northwest China were mostly characterized by "cold, wet, wind, and toxic", and the therapeutic recipes emphasized on the effects of expelling wind and cold, removing toxicity and dampness. Among them, the national plan with the Hubei epidemic situation as an important reference has gradually evolved from a single syndrome attribute of each period to both cold and hot syndromes with multiple treatment methods. With the development of the disease, epidemic toxin and toxic heat in the lungs are the main characteristics in the medium term, when the treatment mainly focuses on purging heat and removing toxins. In severe cases and advanced stage, internal block and outward desertion are the main symptoms, when the treatment mainly focuses on block dredging and relieving desertion. In the recovery period, deficiency of lung and spleen Qi, and deficiency of Qi and Yin are the main symptoms, when the treatment is mainly used to invigorate the spleen, tonify the lungs, and nourish Qi and Yin. The physical factors are mostly reflected in the prevention program, so they are rarely mentioned in the treatment program. The Chinese medicine treatment schemes of COVID-19 in different regions show obvious differences. It is of great significance to analyze these differences and sum up the corresponding laws for the differential prevention and treatment of infectious diseases like COVID-19.

The outbreak of corona virus disease-2019 (COVID-19) not only endangers the public life and health, but also poses threats to the public mental health. Under the atmosphere of tension and fear, the public often produces adverse emotional reactions to psychological stress, and even has extreme behaviors, which seriously affects physical and mental health. Traditional Chinese medicine （TCM） emotional therapy is based on the TCM consciousness theory in adherence to the holistic view of "integration of mind and body". It adopts safe and effective emotional conditioning methods to regulate mood, eliminate bad emotions, maintain mental health, and enhance the body's immunity to achieve the effect of treating or preventing physical and mental diseases. It has differentiated applications in many medical fields, such as post-traumatic stress disorder, generalized anxiety disorder, cancer and hospice, with good clinical efficacy. By analyzing the theoretical origin, research status, application range of TCM sentiment therapy, as well as the current public psychological state of the COVID-19 epidemic, we innovatively proposed TCM sentiment therapies, such as calm emotion method, diversion of attention method, suggestive induction method, obedient mind method, music delight method, TCM refreshing method and auricular pressing method, and comprehensively applied them in the public psychological adjustment during the outbreak, with the aim to provide rational and effective psychological guidance, help the public to correctly understand various bad emotions during the outbreak, enhance their abilities to cope with it and adjust psychological problems, maintain a good mentality, and pass the epidemic period smoothly. At the same time, in order to make better use of the advantages of TCM sentiment therapy and benefit the public, it is advocated to widely apply TCM sentiment therapy in similar public health events and public psychological care in the daily life, for the purpose of preventing before disease outset and preventing progress of disease, and effectively protecting the physical and mental health of the people.

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.
Adolescent ; Betacoronavirus ; Child ; Child, Preschool ; China ; Coronavirus Infections ; Humans ; Infant ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

Objective To assess the current status and factors associated with the mental health condition of older adults. Methods A convenience sampling survey was conducted using symptom check list 90 (SCL-90) among the Chinese older adults aged 60 or above from January to March, 2018. The older adults aged 80 or above were selected for this study. Chi-square test and binary logistic regression model were used to analyze the influencing factors. Results The total participants were 485. The SCL-90 positive detection rate was 20.21%. The symptoms of the four highest detection rates were somatization (39.38%), others (25.15%), obsessive-compulsive symptoms (24.33%) and depression (22.68%). The older adults with normal BMI (OR=0.537, 95% CI: 0.250-0.857, P=0.027) and lived in county town (OR=0.224, 95% CI:0.075-0.667, P=0.007) showed lower SCL-90 positive detection rate. These who had been educated for 1-5 years (OR=11.092, 95% CI: 4.446-27.671, P<0.001), 6-8 years (OR=9.800, 95% CI: 3.464-27.721, P<0.001), 9~11 years (OR=19.279, 95% CI : 6.722-55.297, P<0.001), 12 years and above (OR=24.321, 95% CI: 7.894-74.929, P<0.001) had higher SCL-90 positive detection rate compared with those who were uneducated. Conclusion The mental health condition of Chinese older adults is mainly influenced by residence place, education level, family income self-evaluation and BMI status.