Objective:This study aimed to investigate the association between early immune reconstitution and Epstein-Barr virus (EBV) reactivation by analyzing changes in natural killer (NK), B, and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods:This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation (HSCT). The immune reconstitution of NK cells, T cells, and B cells as well as the expression levels of NK and T cell exhaustion markers (PD-1, TIM-3, and CTLA-4) and cytotoxic function at 1, 2, and 3 months post-transplantation were compared between patients with EBV activation (EBV+ group) and those without activation (EBV- group) post- transplantation.Results:EBV activation occurred in nine patients post-transplantation (EBV+ group), whereas 14 patients demonstrated no activation (EBV- group). All patients with EBV activation exhibited EBV viremia, and no EBV-associated diseases occurred. No significant differences in the clinical characteristics were found between the two groups of patients. The median proportion of CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1 month post-transplantation ( P=0.033). The median proportion of the CD3 -CD16 negCD56 bri subset in the EBV+ group was significantly higher than that in the EBV- group at 2 months post-transplantation ( P=0.046). No significant differences in the median proportions of CD3 -CD19 + B cells were observed between the two groups at 1, 2, and 3 months post-transplantation. The expression of CTLA-4 on CD3 -CD16 briCD56 dim NK cells in the EBV+ group was significantly higher than that in the EBV- group at 1 month post-transplantation ( P=0.033). The expression of TIM-3 on CD3 +CD8 + T cells in the EBV+ group was significantly higher than that in the EBV- group ( P=0.009). The expression level of TIM-3 on CD3 -CD16 negCD56 dim NK cells in the EBV+ group was significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.023). The expression levels of TIM-3 on CD3 +CD4 + T cells in the EBV+ group than those in the EBV- group at 1 and 3 months post-transplantation ( P=0.002, P=0.043). The median positive rate of Granzyme B expression in CD3 +CD8 + T cells and CD3 +CD4 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1-month post-transplantation ( P=0.033, P=0.016). The median positive rate of Granzyme B expression in the CD3 -CD16 briCD56 neg cell subset in the EBV+ group was higher than that in the EBV- group at 2 months post-transplantation ( P=0.012). The median positive rate of Granzyme B expression in CD3 +CD4 + T cells in the EBV+ group remained significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.049). The median positive rate of perforin expression in the CD3 -CD16 briCD56 dim cell subset was significantly higher in the EBV+ group than in the EBV- group at 3 months post-transplantation ( P=0.003). The median positive rate of IFN-γ expression in CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 3 months post-transplantation ( P=0.036) . Conclusion:Delayed NK cell and T lymphocyte reconstitution, high exhaustion marker expression, and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.

Objective:This study aimed to investigate the association between early immune reconstitution and Epstein-Barr virus (EBV) reactivation by analyzing changes in natural killer (NK), B, and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods:This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation (HSCT). The immune reconstitution of NK cells, T cells, and B cells as well as the expression levels of NK and T cell exhaustion markers (PD-1, TIM-3, and CTLA-4) and cytotoxic function at 1, 2, and 3 months post-transplantation were compared between patients with EBV activation (EBV+ group) and those without activation (EBV- group) post- transplantation.Results:EBV activation occurred in nine patients post-transplantation (EBV+ group), whereas 14 patients demonstrated no activation (EBV- group). All patients with EBV activation exhibited EBV viremia, and no EBV-associated diseases occurred. No significant differences in the clinical characteristics were found between the two groups of patients. The median proportion of CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1 month post-transplantation ( P=0.033). The median proportion of the CD3 -CD16 negCD56 bri subset in the EBV+ group was significantly higher than that in the EBV- group at 2 months post-transplantation ( P=0.046). No significant differences in the median proportions of CD3 -CD19 + B cells were observed between the two groups at 1, 2, and 3 months post-transplantation. The expression of CTLA-4 on CD3 -CD16 briCD56 dim NK cells in the EBV+ group was significantly higher than that in the EBV- group at 1 month post-transplantation ( P=0.033). The expression of TIM-3 on CD3 +CD8 + T cells in the EBV+ group was significantly higher than that in the EBV- group ( P=0.009). The expression level of TIM-3 on CD3 -CD16 negCD56 dim NK cells in the EBV+ group was significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.023). The expression levels of TIM-3 on CD3 +CD4 + T cells in the EBV+ group than those in the EBV- group at 1 and 3 months post-transplantation ( P=0.002, P=0.043). The median positive rate of Granzyme B expression in CD3 +CD8 + T cells and CD3 +CD4 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 1-month post-transplantation ( P=0.033, P=0.016). The median positive rate of Granzyme B expression in the CD3 -CD16 briCD56 neg cell subset in the EBV+ group was higher than that in the EBV- group at 2 months post-transplantation ( P=0.012). The median positive rate of Granzyme B expression in CD3 +CD4 + T cells in the EBV+ group remained significantly lower than that in the EBV- group at 2 months post-transplantation ( P=0.049). The median positive rate of perforin expression in the CD3 -CD16 briCD56 dim cell subset was significantly higher in the EBV+ group than in the EBV- group at 3 months post-transplantation ( P=0.003). The median positive rate of IFN-γ expression in CD3 +CD8 + T cells in the EBV+ group was significantly lower than that in the EBV- group at 3 months post-transplantation ( P=0.036) . Conclusion:Delayed NK cell and T lymphocyte reconstitution, high exhaustion marker expression, and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

Child ; Humans ; Inflammatory Bowel Diseases ; Organic Anion Transporters/genetics*

Objective: To explore the types and clinical characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP) based on artificial intelligence and whole-slide imaging (WSI), and to explore the consistency of the diagnostic criteria of the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis (JESREC) in Chinese CRSwNP patients. Methods: The data of 136 patients with CRSwNP (101 males and 35 females, aging 14 to 70 years) who underwent endoscopic sinus surgery from 2018 to 2019 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. The preoperative clinical characteristics of patients were collected, such as visual analogue scale (VAS) of nasal symptoms, peripheral blood inflammatory cell count, total immunoglobulin E (IgE), Lund-Kennedy score and Lund-Mackay score. The proportion of inflammatory cells such as eosinophils, lymphocytes, plasma cells and neutrophils were calculated on the WSI of each patient through artificial intelligence chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0), and the specific type of nasal polyps was then obtained as eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (non-eCRSwNP). In addition, the JESREC diagnostic criteria was used to classify the nasal polyps, and the classification results were compared with the current gold standard for nasal polyps diagnosis (pathological diagnosis based on WSI). The accuracy, sensitivity and specificity of the diagnostic criteria of JESREC were evaluated. The data were expressed in M (Q₁, Q₃) and statistically analyzed by SPSS 17.0. Results: There was no significant difference between eCRSwNP and non-eCRSwNP in age distribution, gender, time of onset, total VAS score, Lund-Kennedy score or Lund-Mackay score. However, there was a significant difference in the ratio of nasal polyp inflammatory cells (eosinophils 40.5% (22.8%, 54.7%) vs 2.5% (1.0%, 5.3%), neutrophils 0.3% (0.1%, 0.7%) vs 1.3% (0.5%, 3.6%), lymphocytes 49.9% (39.3%, 65.9%) vs 82.0% (72.8%, 87.5%), plasma cells 5.1% (3.6%, 10.5%) vs 13.0% (7.4%, 16.3%), χ² value was 9.91, 4.66, 8.28, 5.06, respectively, all P<0.05). In addition, eCRSwNP had a significantly higher level of proportion of allergic symptoms (nasal itching and sneezing), asthma, peripheral blood eosinophil and total IgE (all P<0.05). The overall accuracy, sensitivity and specificity of the JESREC diagnostic criteria was 74.3%, 81.3% and 64.3%, respectively. Conclusions: The eCRSwNP based on artificial intelligence and WSI has significant high level of allergic symptoms, asthma, peripheral blood eosinophils and total IgE, and the percentages of inflammatory cells in nasal polyps are different from that of non-eCRSwNP. The JESREC diagnostic criteria has good consistency in our research.
Artificial Intelligence ; Chronic Disease ; Eosinophils/metabolism* ; Female ; Humans ; Male ; Nasal Polyps/pathology* ; Retrospective Studies ; Rhinitis/pathology* ; Sinusitis/pathology*

Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.
Ageusia ; Big Data ; COVID-19 ; Disease Outbreaks ; Humans ; Internet ; Retrospective Studies ; Smell ; United States

Radix Astragali (RA), a traditional Chinese medicine from the dried root of Astragalus species, is widely distributed throughout the temperate regions of the world. The major bioactive constituents of RA are triterpene glycosides, flavonoids, saponins, and alkaloids, and these compounds mostly exert pharmacological activities on the cardiovascular, immune, respiratory, and hepatic systems. This review summarizes the recent studies on RA and provides a comprehensive summary regarding the status of resources, ethnopharmacology, phytochemistry, pharmacology, toxicology, clinical application, and patent release of RA. We hope this review can provide a guidance for further development of therapeutic agents from RA.

Objective To analyze the epidemiological characteristics of COVID-19 cases reported in Xianyang City from January to February 2020. Methods We retrospectively studied 17 COVID-19 patients diagnosed in Xianyang Central Hospital. The patients were characterized clinically and epidemiologically. Results The 17 patients included 10 male and 7 female, with an average age of(39.59±17.31)years. The median interval of time between onset and diagnosis was four days(1-10 days), whereas the median duration of COVID-19 was 16 days(3-23 days). Of the patients, six were mild, 10 were pneumonia, and one was severe. A total of 15 patients had fever as the onset, accompanied by fatigue, sore throat, sputum, vomit, muscle soreness; the other two patients were asymptomatic. There were no complications documented in all the patients. Patients had low levels of white blood cells and lymphocytes. Chest CT scan showed diverse diffuse ground-glass shadow. Eleven patients had travel history in Wuhan before the onset, four patients had contact with people who had travel history or residence history in Wuhan, and the other two patients did not report epidemiological exposure history. In addition, four of the 17 patients were clustered cases. Conclusion General population is susceptible to COVID-19. The majority of the confirmed cases have epidemiological exposure history. Routine examination, including white blood cell, lymphocyte count and CT scan may facilitate early diagnosis.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

COVID-19/virology* ; China/epidemiology* ; Cross Infection/virology* ; Fever/virology* ; Health Personnel/statistics & numerical data* ; Hospitals, Isolation/statistics & numerical data* ; Humans ; SARS-CoV-2/isolation & purification*