Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Highly Tunable MOF Luminophores Featuring Anthracene Directed Assembly and Fluorescence Regulation.

Metal-organic frameworks (MOFs) have been recognized as a potential platform for the development of tunable luminophores owing to their highly modulable structures and components. Herein, two MOF luminophores based on Cd(II) ions, 1,3,5-tri(4-pyridinyl)benzene (TPB), and 1,4-dicarboxybenzene (H2BDC) were constructed. The directed assembly of the metal ions and organic linkers results in [Cd2(BDC)2(TPB)(H2O)]·x(solvent) (MOF-1) featuring TPB-based blue fluorescence centered at 425 nm. By introducing anthracene as the structure directing agent (SDA) for assembly regulation, [Cd2(BDC)(TPB)2(NO3)2]·x(solvent) (MOF-2) was obtained, which reveals anthracene feeding-dependent high tunable emission in the 517-650 nm range. Detailed components, photophysical properties, and structural characteristics investigations of MOF-2 indicate the TPB and NO3- interactions as the origin of its redshifted emission compared with that of MOF-1. Furthermore, the fluorescence of MOF-2 was found to be regulatable by the anthracene feeding based on the SDA-determined crystallinity of the crystalline sample. All these results provided a unique example of the structural and fluorescence regulation of MOF luminophores.

Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis.

BACKGROUND: The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. METHODS: Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People's Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-ß1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. RESULTS: The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-ß1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-ß1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). CONCLUSIONS: Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-ß1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Chalcones from plants cause toxicity by inhibiting human and rat 11ß-hydroxysteroid dehydrogenase 2: 3D-quantitative structure-activity relationship (3D-QSAR) and in silico docking analysis.

Chalcones from licorice and its related plants have many pharmacological effects. However, the effects of chalcones on the activity of human and rat 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), and associated side effects remain unclear. The inhibition of 11 chalcones on human and rat 11ß-HSD2 were evaluated in microsomes and a 3D-quantitative structure-activity relationship (3D-QSAR) was analyzed. Screening revealed that bavachalcone, echinatin, isobavachalcone, isobavachromene, isoliquiritigenin, licochalcone A, and licochalcone B significantly inhibited human 11ß-HSD2 with IC50 values ranging from 15.62 (licochalcone A) to 38.33 (echinatin) µM. Screening showed that the above chemicals and 4-hydroxychalcone significantly inhibited rat 11ß-HSD2 with IC50 values ranging from 6.82 (isobavachalcone) to 72.26 (4-hydroxychalcone) µM. These chalcones acted as noncompetitive/mixed inhibitors for both enzymes. Comparative analysis revealed that inhibition of 11ß-HSD2 depended on the species. Most chemicals bind to the NAD+ binding site or both the NAD+ and substrate binding sites. Bivariate correlation analysis showed that lipophilicity and molecular weight determine inhibitory strength. Through our 3D-QSAR models, we identified that the hydrophobic region, hydrophobic aliphatic groups, and hydrogen bond acceptors are pivotal factors in inhibiting 11ß-HSD2. In conclusion, many chalcones inhibit human and rat 11ß-HSD2, possibly causing side effects and there is structure-dependent and species-dependent inhibition on 11ß-HSD2.

[A research of Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus based on experts' questionnaires].

OBJECTIVE: To establish Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus. METHODS: A Chinese medicine diagnosis and treatment standard procedure for patients with HIV associated pruritus was established by literature retrieval and peer review. Two questionnaires were carried out to investigate the confirmation and advice of in-group specialists to key points of the draft including diagnosis, treatment and nursing. Then the procedures were revised accordingly. RESULTS: The recovery rate of complete questionnaires in the 1st survey was 96%. Specialists confirmed more on case history and physical examinations, syndrome differentiation of three syndrome types, treatment of blood deficiency wind dryness syndrome (BDWDS) and nursing. They held different opinions on the outlines, auxiliary examinations, treatment of blood heat induced wind evil syndrome (BHWES) and wind cold and dampness accumulation syndrome (WCDAS), of which the coefficient of variations (CVs) was within 0.1603 -0.2473. The procedures were revised and the 2nd survey was launched. The recovery rate of complete questionnaires in the 2nd survey was 100%. Specialists confirmed more on case history and physical examinations, diagnostic criteria, syndrome differentiation of BDWDS and WCDAS, and treatment of BDWDS, of which CVs was 0. All indicated high agreement and good compliance. The CVs of other items were within 0.0638-0.1439, less than those of the 1st survey. The consistency of experts' opinions were somewhat improved. The contribution by one single item showed less difference in assessing the overall results in the two surveys. A new revision of the procedure was preliminarily established according to results of two surveys. CONCLUSIONS: Experts' activeness, concentration, and coordination were good in the two surveys. They had reached consensus in key points of the draft including diagnosis, treatment, and nursing.

Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection in China was documented on May 10. Subsequently, persons with suspected cases of infection and contacts of those with suspected infection were tested. Persons in whom infection was confirmed were hospitalized and quarantined, and some of them were closely observed for the purpose of investigating the nature and duration of the disease. METHODS: During May and June 2009, we observed 426 persons infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in 61 hospitals in 20 provinces. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored, and 254 patients were treated with oseltamivir within 48 hours after the onset of disease. RESULTS: The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours. CONCLUSIONS: Surveillance of the 2009 H1N1 virus in China shows that the majority of those infected have a mild illness. The typical period during which the virus can be detected with the use of real-time RT-PCR is 6 days (whether or not fever is present). The duration of infection may be shortened if oseltamivir is administered.

Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

BACKGROUND: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING: Eleven hospitals from 4 provinces in China. PATIENTS: 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE: Beijing Science and Technology Project and Beijing Nova Program.

Duration of viral shedding of influenza A (H1N1) virus infection treated with oseltamivir and/or traditional Chinese medicine in China: a retrospective analysis.

OBJECTIVE: H1N1 was a new and potentially serious infectious disease, in human, the severity of influenza can vary from mild to severe, thus to find an effective and safety way to control the influenza pandemic is of crucial importance. This retrospective study describes the duration of viral shedding in H1N1 patients that were hospitalized and treated in China. METHODS: Clinical data were collected from May to July, 2009 in China for 963 patients with influenza A (H1N1) virus infection. Patients were treated based on the guidelines issued by the Chinese Ministry of Health. The primary outcome was duration of viral shedding and statistical comparisons were performed. RESULTS: In the patients with body temperature greater than 38.0 degrees C, there were no differences in virus shedding duration among the patients taking oseltamivir within two days, patients undergoing Traditional Chinese Medicine (TCM) therapy or those receiving no drug therapy. In patients with body temperature > or =38.1 degrees C, TCM therapy reduced the viral shedding duration (P < 0.05, vs. oseltamivir therapy). Furthermore, taking oseltamivir two days after onset of symptoms might prolong the virus shedding duration (P < 0.05, vs. taking oseltamivir less than 2 days of onset). CONCLUSION: TCM therapy is effective for reducing the length of virus shedding in patients with body temperature > or =38.0 degrees C. Oseltamivir used for reducing virus shedding duration should be taken within two days of onset.

Accelerated Aging of T-Cell Subsets Among ART-Naïve HIV-Infected Chinese Men Who have Sex with Men: A Case-Control Study.

BACKGROUND: Evidence of lymphopoiesis, exhaustion, and premature aging in Chinese patients with human immunodeficiency virus (HIV) is very limited. OBJECTIVE: To assess biological aging and immune senescence in Chinese healthy controls (HC) and ART-naïve HIV-infected men who have sex with men (MSM). METHODS: This case-control study was conducted in Beijing Ditan Hospital from March 2018 to June 2019. The percentages of naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated memory (TemRA) subsets of CD4 and CD8 T cells were studied, along with markers of senescence (CD28-CD57+) and activation (HLA-DR+). Telomere length of naïve (CD45RA+) and memory (CD45RO+) CD8 T cells were quantified by real-time PCR. RESULTS: A total of 26 HIV-infected and 20 age-matched HC MSM were included. Compared to the HC group, the CD4/CD8 ratio of the HIV-infected group was significantly reduced (0.30 vs. 1.70, P<0.001); significant differences emerged among all CD8 but not CD4 T cell subsets (all P<0.05). In the HIV-infected group, the percentages of senescent cells (CD28-CD57+) in TN, TCM, TEM, and TemRA subsets of CD8 T cells were higher (all P<0.05); while a significant difference was only found in naïve CD4 T cells (P<0.05). HLA-DR expression was increased significantly in all CD4 and CD8 T cell subsets. Both naïve (CD45RA+) and memory (CD45RO+) CD8 T cells in this population had significantly shorter telomere lengths (P<0.01) compared to the HC group. CONCLUSION: HIV-infected MSM exhibit signs of accelerated immune senescence and biological aging, which particularly affects the CD8 T-cell subsets.

[The pathogenic analysis of 120 acquired immune deficiency syndrome patients with pulmonary infections via bronchoscopy].

OBJECTIVE: To evaluate the clinical value of bronchoscopy in the pathogenic diagnosis of AIDS patients with pulmonary infections and to illustrate the constituent ratio of different pulmonary pathogens. METHODS: From August 2006 to September 2009, we performed bronchoscopies to 120 AIDS patients who had pulmonary infections. We described the manifestations under the bronchoscope and each patient underwent bronchoalveolar lavage for further detection including bacterial culture and pathological test. We also took biopsies in patients who had obviously abnormal lesions under the bronchoscope.At the same time, we collected the clinical information for analyzing. RESULTS: Among 120 patients, we found 30 cases of mycobacteria infection, 25 cases of bacterial infection, 12 cases of PCP, 5 cases of fungal positive, 3 cases of CMV. Bronchial mucosa biopsies were taken in 26 patients, 12 cases of chronic inflammation, 7 cases of granulomatous inflammation, 4 cases of squamous cell carcinoma, 2 cases of adenocarcinoma and 1 case of lymphoma. CONCLUSION: Bronchoscopy is a very useful tool and it's of great value for pathogenic detection in AIDS patients with pulmonary infections. At present, in China the main pulmonary infections in AIDS patients are TB, bacterial infection and PCP.

[The analysis of the clinical features between survivors and non-survivors with the severe form of new influenza A (H1N1) viral infection].

OBJECTIVE: To understand the clinical features of critically ill patients with pandemic 2009 influenza A (H1N1) and investigate the risk factors associated with death cases. METHODS: The clinical features of 55 critically ill patients with pandemic 2009 influenza A (H1N1) viral infection hospitalized at Beijing Ditan Hospital from October 3 to December 15, 2009 were retrospectively analyzed, and a comparative analysis was performed on the manifestations of the survival and the death groups of patients. RESULTS: There were 31 males and 24 females. The age ranged from 10 months to 84 year old, and the mean (SD) was 38 (20) year old. The critically ill cases were more in patients under age 65 (48/55), with obesity (33/49), with underlying diseases (26/49), and pregnancy (6/24). Both the survivors and non-survivors of patients had high fever, cough, sputum (some sputum with blood), dyspnea, räles of both lungs fields, and all further developed severe pneumonia. The patients also showed respiratory failure (54/55) and ARDS (26/55). All of them received oseltamivir therapy, and 38 patients received mechanical ventilation and 30 were given steroid therapy. Secondary infection occurred in 27 cases, and ventilator-associated pneumonia happened in 10 patients. In the early stage of onset, C-reactive protein (CRP) increased [(131 ± 130) mg/L] and low counts of T lymphocytes were present [CD(4)(+), CD(8)(+) T was (217 ± 139)/µl and (162 ± 82)/µl]. With the progress of disease, the non-survival cases had persistently increased CRP and the counts of T lymphocytes did not recover, while the secondary fungal infection was significantly higher than in the survivor cases (P < 0.05). By using BMI, underlying diseases, ARDS, the day of Oseltamivir initiated, steroid therapy, following bacterial and fungal infection as variables through logistic regression analysis, it was shown that higher BMI and following fungal infection were associated with higher fatal risks (OR was 6.512, 19.631 respectively, both of P value was low than 0.05). There was no death case who received oseltamivir treatment within 48 hours of onset of disease. CONCLUSIONS: Critical illness in pandemic 2009 influenza A (H1N1) was associated with patients under age 65, with obesity, underlying diseases, and pregnancy. Persistently increased CRP and lower counts of T lymphocytes were associated with unfavorable prognosis. The patients with higher BMI and secondary fungal infection had higher fatal risks. Oseltamivir treatments at early stage would probably reduce mortality.

Soluble IL-2Rα correlates with imbalances of Th1/Th2 and Tc1/Tc2 cells in patients with acute brucellosis.

BACKGROUND: Previous studies showed that soluble IL-2Rα is an important marker of cellular immune activation and might be a marker of treatment efficacy for children with brucellosis. However, data regarding adult patients with brucellosis were unknown. The aim of study was to explore the potential role of serum sIL-2Rα evaluating treatment responses in adult patients with brucellosis, and T cell immune status was also examined. METHODS: During January 2016-April 2017, 30 patients with acute brucellosis from the Third People's Hospital of Linfen in Shanxi Province and Beijing Di Tan Hospital, and 28 healthy controls were included in this study. Peripheral blood samples were collected before and after six weeks of antibiotic treatment. Serum sIL-2Rα levels were measured by enzyme-linked immunosorbent assay, and the percentage of Th1, Th2, Tc1, Tc2, and Tregs was detected by flow cytometry after intracellular staining for cytokines (interferon-γ and interleukin-4) and Foxp3 in T lymphocytes from peripheral blood. The obtained data were analyzed with Wilcoxon ranked sum tests for paired values, Mann-Whitney U-tests for comparisons between patients and healthy controls, and Spearman rank tests for correlation analyses. RESULTS: Serum sIL-2Rα levels were significantly higher in patients than in controls (P = 0.001). A significant decline was observed in patients after the cessation of treatment (P < 0.001) and return to normal (P > 0.05). Th1, Tc1, Th2, and Tc2 cell frequencies were higher in patients than in healthy subjects (P < 0.05), while the Th1/Th2 and Tc1/Tc2 ratios were significantly lower (P = 0.0305 and 0.0005, respectively) and returned to normal levels after treatment. In patients with acute brucellosis, serum sIL-2Rα levels were negatively correlated with the Th1/Th2 ratio (r = - 0.478, P = 0.028), Tc1/Tc2 ratio (r = - 0.677, P = 0.001), and Tc1 percentage (r = - 0.516, P = 0.017). Serum sIL-2Rα and Tc2 percentages were positively correlated (r = 0.442, P = 0.045). CONCLUSIONS: Based on the correlations with Th1/Th2 and Tc1/Tc2 ratios, serum sIL-2Rα levels may reflect the immune response status. sIL-2Rα may be a marker for therapeutic efficacy in acute brucellosis.

Bibliometric analysis of randomized controlled trials of colorectal cancer over the last decade.

BACKGROUND: Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM: To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS: PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS: Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION: High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11beta-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells.

Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), not 11beta-HSD1, is strongly expressed in murine gonadotrope LbetaT2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11beta-HSD2 enzyme activity in LbetaT2 cells at as low as 10(-7)M. Corticosterone (CORT) at a concentration of 10(-6)M significantly inhibited LbetaT2 cell proliferation after 2-day culture, and 10(-6)M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10(-5) or 10(-4)M MEHP, the minimal concentration of CORT to inhibit the proliferation of LbetaT2 cells was lowered to 10(-7)M, and 10(-6)M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11beta-HSD2 may have a key role in glucocorticoid metabolism in LbetaT2 cells. MEHP may participate in the glucocorticoid metabolism in LbetaT2 cells through inhibition of 11beta-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure.