The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker.

BACKGROUND: The role of the macrophage migration inhibitory factor (MIF) has recently attracted considerable attention in cancer research; nonetheless, the insights provided by current investigations remain constrained. Our main objective was to investigate its role and the latent mechanisms within the pan-cancer realm. METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool. RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions. CONCLUSION: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.

[Simultaneous determination of seven artemisinin-related compounds in Artemisia annua by UPLC-QQQ-MS/MS].

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

The interaction effect of depressive symptoms and inflammation on the occurrence of cardiovascular diseases.

BACKGROUND: Whether there was an interaction effect between depressive symptoms and inflammation on the occurrence of cardiovascular diseases (CVDs) was unclear. METHODS: In this cross-sectional study, 3346 participants in the National Health and Nutrition Examination Survey (NHANES) were included. Multivariable regression analysis was performed to explore the associations of depressive symptoms or inflammation with CVDs. The attributable proportion of interaction (API), and synergy index (SI) were applied for evaluating the statistical significance of the interaction effect. RESULTS: Depressive symptoms were associated with 2.31-fold risk of CVDs [odds ratio (OR) = 2.31, 95 % confidence interval (CI): 1.47-3.62). The increased risk of CVDs was observed in people with neutrophil to lymphocyte ratio (NLR) ≥1.88 group (OR = 1.36, 95%CI: 1.01-1.85) and neutrophil/[white blood cell (WBC)-neutrophil] ≥1.35 (OR = 1.52, 95%CI: 1.12-2.07) after adjusting for confounders. The interaction effect of depressive symptoms and high NLR on the risk of CVDs was statistically significant with an OR value of 2.60 (95%CI: 1.43-4.70) compared to low NLR and no depressive symptoms group after adjusting for confounders. The API was 0.66 (95%CI: 0.44-0.89) and SI was 4.23 (95%CI: 2.08-8.59). The interaction effect of depressive symptoms and high neutrophil/(WBC-neutrophil) was associated with the risk of CVDs compared to low neutrophil/(WBC-neutrophil) and no depressive symptoms group (OR = 3.59, 95%CI: 2.00-6.45). The API was 0.78 (95%CI: 0.63-0.93) and SI was 6.75 (95%CI: 3.55-12.82). CONCLUSION: There was an interaction effect of depressive symptoms and inflammation on the occurrence of CVDs.

Association between prehospital time and in-hospital outcomes in out-of-hospital cardiac arrests according to resuscitation outcomes consortium epidemiologic registry.

INTRODUCTION: For out-of-hospital cardiac arrests (OHCAs), time is of the essence. While the relationship between EMS response time (ERT) and OHCA outcomes is well studied, a more comprehensive assessment of the effects of other intervention time is needed, which is essential to guide clinical practice. OBJECTIVES: Evaluating how a longer total pre-hospital time (TPT), ERT, advance life support response time (ART) and EMS cardiopulmonary resuscitation time (ECT) increase the mortality rates, unfavorable neurological outcomes, and severe complications at discharge of OHCAs. METHODS: 31,926 OHCAs from the USA and Canada were identified in Resuscitation Outcomes Consortium Epidemiologic Registry. Twelve adjusted models were used to analyze the relationship between the prehospital time (TPT, ERT, ART and ECT) and three outcomes (in hospital mortality, unfavorable neurological outcomes, and severe complications for surviving OHCAs). RESULTS: Every 10-min increase in TPT was associated with a 0.14-fold increase in the risk of death (adjusted odds ratio [OR] = 1.14, 95 % confidence interval [CI] = 1.10-1.17) and a 0.13-fold increase of adverse neurological outcomes (OR = 1.13, CI =1.08-1.18). The risk of patient mortality markedly increased with every 5 min increase in ERT (OR = 1.36, CI = 1.26-1.47), ART (OR =1.10, CI = 1.06-1.15), and ECT (OR = 1.46, CI = 1.37-1.56). Adverse neurological outcome was associated with ERT and ECT, and severe complications with ERT and ART. CONCLUSION: Prolonged prehospital time, particularly ERT and ECT, are closely associated with in-hospital mortality, unfavorable neurological functions, and severe complications at discharge in OHCAs.

Association of clinical characteristics and vaccines with risk of persistently viral clearance in patients infected with SARS-CoV-2 Omicron variant in Shanghai, China.

Importance: The global COVID-19 pandemic does not appear to end in the near future. Currently, limited data are available on the risk factors for delayed viral clearance in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Objective: This study aimed to investigate the association of clinical characteristics and vaccination with prolonged viral clearance. Methods: This retrospective cohort included 16,985 patients who had contracted the SARS-CoV-2 Omicron variant between April 5 and May 30, 2022, in Shanghai, China, and had mild or no symptoms. The patients were admitted to the quarantine venue at the Shanghai New International Expo Center. Results: Of the 16,985 participants, the occurrence of viral clearance was ≤8 and > 8 days in 11,009 (64.8 %) and 5976 (35.2 %) participants, respectively. Risk factors related to patients who remained persistently polymerase chain reaction (PCR)-positive were sex (Male, odds ratio [OR] 1.221, p < 0.001), older age (35-49, OR 1.389, p < 0.001; 50-64, OR 1.659, p < 0.001; ≥65, OR 2.139, p < 0.001), presence of symptoms (OR 1.093, p = 0.030), number of vaccinations (two doses, OR 0.753, p < 0.001; three doses, OR 0.797, p < 0.001; four doses, OR 0.543, p < 0.001), and cycle threshold (Ct) value for ORF1ab gene at diagnosis (25-35, OR 0.235, p < 0.001; >35, OR 0.079, p < 0.001). The lower rates of increase in Ct values were observed in the later viral shedding group than in the early viral shedding group for ORF1ab (ß = -0.791, p < 0.001) and N genes (ß = -0.825, p < 0.001). Conclusion: Prolonged SARS-CoV-2 RNA detection and higher viral concentrations were associated with factors such as male sex, older age, symptomatic status, and fewer doses of vaccination in patients admitted to Shanghai Makeshift Hospital between April 5 and May 30, 2022.

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).

Racial and ethnic disparities in bystander resuscitation for out-of-hospital cardiac arrests.

INTRODUCTION: Bystander-provided cardiopulmonary resuscitation (CRP) influences the survival rates of out-of-hospital cardiac arrests (OHCAs). Disparities on bystander resuscitation measures between Black, Hispanic, Asians and Non-Hispanic White OHCAs is unclear. Examining racial and ethnic differences in bystander resuscitations is essential to better target interventions. METHODS: 15,542 witnessed OHCAs were identified between April 1, 2011, and June 30, 2015 using the Resuscitation Outcomes Consortium Epidemiologic Registry 3, a multi-center, controlled trial about OHCAs in the United States and Canada. Multivariable logistic regression model was used to analyze the differences in bystander resuscitation (bystander CRP [B-CPR], CPR plus ventilation, automated external defibrillators/defibrillator application [B-AED/D], or delivery of shocks) and clinical outcomes (death at the scene or en route, return of spontaneous circulation upon first arrival at the emergency department [ROSC-ED], survival until ED discharge [S-ED], survival until hospital discharge [S-HOS], and favorable neurological outcome at discharge) between Black, Hispanic, or Asian victims and Non-Hispanic White victims. RESULTS: Compared to OHCA victims in Non-Hispanic Whites, Black, Hispanic, and Asians were less likely to receive B-CPR (adjusted OR: 0.79; 95 % CI: 0.63-0.99), and B-AED/D (adjusted OR: 0.80; 95 % CI: 0.65-0.98) in public locations. And, Black, Hispanic, and Asian OHCAs were less likely to receive bystander resuscitation in street/highway locations and public buildings, and less likely to have better clinical outcomes, including ROSC-ED, S-ED and S-HOS. CONCLUSION: Black, Hispanic and Asian victims with witnessed OHCAs are less likely to receive bystander resuscitation and more likely to get worse outcomes than Non-Hispanic White victims.

Higher plasma aldosterone concentrations in patients with aortic diseases and hypertension: a retrospective observational study.

BACKGROUND: Aortic diseases remain a highly perilous macrovascular condition. The relationship between circulating aldosterone and aortic diseases is rarely explored, thus we investigated the difference in plasma aldosterone concentration (PAC) between patients with and without aortic disease in hypertensive people. METHODS: We analyzed 926 patients with hypertension, ranging in age from 18 to 89 years, who had their PAC measured from the hospital's electronic database. The case group and control group were defined based on inclusion and exclusion criteria. The analysis included general information, clinical data, biochemical data, and medical imaging examination results as covariates. To further evaluate the difference in PAC between primary hypertension patients with aortic disease and those without, we used multivariate logistic regression analysis and also employed propensity score matching to minimize the influence of confounding factors. RESULTS: In total, 394 participants were included in the analysis, with 66 individuals diagnosed with aortic diseases and 328 in the control group. The participants were predominantly male (64.5%) and over the age of 50 (68.5%), with an average PAC of 19.95 ng/dL. After controlling for confounding factors, the results showed hypertension patients with aortic disease were more likely to have high PAC levels than those without aortic disease (OR = 1.138, 95% CI [1.062 to 1.238]). Subgroup analysis revealed consistent relationship between PAC and primary hypertensive patients with aortic disease across the different stratification variables. Additionally, hypertensive patients with aortic disease still have a risk of higher PAC levels than those without aortic disease, even after propensity score matching. CONCLUSIONS: The results of this study suggest that primary hypertensive patients with aortic diseases have elevated levels of PAC, but the causal relationship between PAC and aortic disease requires further study.

Predictive value of risk factors for prognosis of patients with sepsis in intensive care unit.

Sepsis has emerged as a major global public health concern due to its elevated mortality and high cost of care. This study aimed to evaluate the risk factors associated with the mortality of sepsis patients in the Intensive Care Unit (ICU), and to intervene in the early stages of sepsis in order to improve patient outcomes and reduce mortality. From January 1st, 2021 to December 31st, 2021, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Huashan Hospital Affiliated to Fudan University, and The Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine were designated as sentinel hospitals, and sepsis patients in their respective ICU and Emergency ICU were selected as research subjects, and divided into survivors and non-survivors according to their discharge outcomes. The mortality risk of sepsis patients was subsequently analyzed by logistic regression. A total of 176 patients with sepsis were included, of which 130 (73.9%) were survivors and 46 (26.1%) were non-survivors. Factors identified as having an impact on death among sepsis patients included female [Odds Ratio (OR) = 5.135, 95% confidence interval (CI): 1.709, 15.427, P = .004)], cardiovascular disease (OR = 6.272, 95% CI: 1.828, 21.518, P = .004), cerebrovascular disease (OR = 3.133, 95% CI: 1.093, 8.981, P = .034), pulmonary infections (OR = 6.700, 95% CI: 1.744, 25.748, P = .006), use of vasopressors (OR = 34.085, 95% CI: 10.452, 111.155, P < .001), WBC < 3.5 × 109/L (OR = 9.752, 95% CI: 1.386, 68.620, P = .022), ALT < 7 U/L (OR = 7.672, 95% CI: 1.263, 46.594, P = .027), ALT > 40 U/L (OR = 3.343, 95% CI: 1.097, 10.185, P = .034). Gender, cardiovascular disease, cerebrovascular disease, pulmonary infections, the use of vasopressors, WBC, and ALT are important factors in evaluating the prognostic outcome of sepsis patients in the ICU. This suggests that medical professionals should recognize them expeditiously and implement aggressive treatment tactics to diminish the mortality rate and improve outcomes.

Hemolysis associated with Russula subnigricans ingestion in a patient with glucose-6-phosphate dehydrogenase deficiency.

INTRODUCTION: Russula subnigricans is now one of the leading lethal mushroom species in China, with a mortality rate of more than 50%. The typical clinical manifestation of Russula subnigricans poisoning is rhabdomyolysis, and we are unaware of previous reports of Russula subnigricans-associated hemolysis. CASE SERIES: Herein we report a cluster of five patients with confirmed Russula subnigricans poisoning. Four of the patients who ingested sun-dried Russula subnigricans never developed rhabdomyolysis. However, in one patient, acute hemolysis developed on the second day following ingestion and was associated with a fall in hemoglobin concentration and a rise in unconjugated bilirubin concentration. Further investigation revealed that the patient had glucose-6-phosphate dehydrogenase deficiency. CONCLUSION: This case cluster suggests that the toxin of Russula subnigricans could cause hemolysis in a susceptible patient and warrants further study.

The Classification, Molecular Structure and Biological Biosynthesis of Flavonoids, and Their Roles in Biotic and Abiotic Stresses.

With the climate constantly changing, plants suffer more frequently from various abiotic and biotic stresses. However, they have evolved biosynthetic machinery to survive in stressful environmental conditions. Flavonoids are involved in a variety of biological activities in plants, which can protect plants from different biotic (plant-parasitic nematodes, fungi and bacteria) and abiotic stresses (salt stress, drought stress, UV, higher and lower temperatures). Flavonoids contain several subgroups, including anthocyanidins, flavonols, flavones, flavanols, flavanones, chalcones, dihydrochalcones and dihydroflavonols, which are widely distributed in various plants. As the pathway of flavonoid biosynthesis has been well studied, many researchers have applied transgenic technologies in order to explore the molecular mechanism of genes associated with flavonoid biosynthesis; as such, many transgenic plants have shown a higher stress tolerance through the regulation of flavonoid content. In the present review, the classification, molecular structure and biological biosynthesis of flavonoids were summarized, and the roles of flavonoids under various forms of biotic and abiotic stress in plants were also included. In addition, the effect of applying genes associated with flavonoid biosynthesis on the enhancement of plant tolerance under various biotic and abiotic stresses was also discussed.

Metabolic profiling and transcriptome analysis provide insights into the accumulation of flavonoids in chayote fruit during storage.

Chayote (Sechium edulel) fruits are rich in flavonoids, folate, and low-calorie food. However, studies about the flavonoids and the corresponding regulatory mechanism of flavonoid synthesis in chayote fruits was still unclear. In present study, an integrated transcriptome and metabolite analysis of chayote fruits at three different storage stages were conducted to explore the flavonoid compositions and gene expression associated with flavonoid synthesis. Through the UPLC-MS/MS analysis, a total of 57 flavonoid compounds were detected. Of these, 42 flavonoid glycosides were significantly differential accumulation in chayote fruits at three different storage stages. Many genes associated with flavonoid synthesis were differentially expressed in chayote fruits at three different storage stages through RNA-seq analysis, including structural genes and some TFs. There was a high correlation between RNA-seq analysis and metabolite profiling, and the expression level of candidate genes in the flavonoid synthesis pathway were consistent with the dynamic changes of flavonoids. In addition, one R2R3-MYB transcription factor, FSG0057100, was defined as the critical regulatory gene of flavonoid synthesis. Furthermore, exogenous application of phenylalanine increased the total content of flavonoids and promoted some flavonoid biosynthesis-related gene expression in chayote fruits. The above results not only make us better understand the molecular mechanism of flavonoid synthesis in chayote fruits, but also contribute to the promotion and application of chayote products.

Efficacy of Lianhua Qingwen for children with SARS-CoV-2 Omicron infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Lianhua Qingwen Granules or Capsules (LHQW) has accumulated much research evidence in the fight against the coronavirus disease 2019 (COVID-19) epidemic. However, there are still few data on its efficacy and safety in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PURPOSE: To evaluate the efficacy and safety of LHQW in children with SARS-CoV-2 Omicron infection. METHODS: We conducted a single-center, propensity-score matched retrospective cohort study of children with SARS-CoV-2 Omicron infection in Shanghai New International Expo Center mobile cabin hospital between April 1st and June 1st, 2022. Eligible patients received either LHQW granules/capsules plus supportive care (LHQW group) or supportive care alone (control group). The primary outcome was the negative conversion time of nucleic acid. Secondary outcomes included the negative conversion rate of nucleic acid, the length of hospital stay, clinical disease progression, and cycle threshold [Ct] values for SARS-CoV-2 open reading frame [ORF1ab] or nucleocapsid [N] genes. RESULTS: Overall, 2808 patients were enrolled, and 346 patients in each group were included in the analysis. Among the propensity-score matched groups, LHQW treatment was associated with an accelerated negative conversion time of nucleic acid (median: 5 d vs. 6 d, Hazard ratio: 1.25, 95% CI: 1.08 - 1.46, Log-rank p < 0.001), a higher negative conversion rate of nucleic acid (Day 2 - 6: 2.9% vs. 0.6%, p = 0.036; 29.8% vs. 5.5%, p < 0.001; 42.5% vs. 24.3%, p < 0.001; 51.4% vs. 31.5%, p < 0.001; 63.3% vs. 55.2%, p = 0.030), shorter hospital stay (median: 10 d vs. 11 d, Hazard ratio: 1.50, 95% CI: 1.29 - 1.74, Log-rank p < 0.001), and lower rates of asymptomatic infection progressing to mild (37.9% vs. 46.5%, p = 0.021). CONCLUSION: Our study suggested that LHQW treatment was associated with faster clinical recovery in children with SARS-CoV-2 Omicron infection.

Efficacy and safety of Reyanning mixture in patients infected with SARS-CoV-2 Omicron variant: A prospective, open-label, randomized controlled trial.

BACKGROUND: A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. STUDY DESIGN AND METHODS: This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. RESULTS: A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. CONCLUSION: RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

Clinical predictors and RT-PCR profile of prolonged viral shedding in patients with SARS-CoV-2 Omicron variant in Shanghai: A retrospective observational study.

Objective: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods: Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, "early clearance" and ≥15 days, "late clearance"). Results: 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion: The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.

Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking.

OBJECTIVE: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology. METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets. RESULTS: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase. CONCLUSION: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.

An Epidemiological Study on the Relationship between Drug Control Program and Patient Compliance in Elderly Patients with Hypertension.

Objective: To explore the relationship between medication control regimen and patient compliance in elderly hypertensive patients. Methods: A retrospective analysis of 1432 elderly hypertensive patients in our hospital from February 2020 to February 2021 was conducted. The general data of patients, the drug control regimen, the occurrence of drug side effects, and blood pressure control of patients during hospitalization and outpatient follow-up were statistically analyzed. Results: The first dose rate was higher in patients given a single dose during hospitalization than in patients followed up in outpatient clinics, and the discharge rate was lower than for single doses (P < 0.05). Patients had a lower first dose rate and a higher discharge rate for the two drug combinations during hospitalization compared to outpatient follow-up patients, while the first dose rate and discharge rate were significantly lower during hospitalization. Three drugs were administered (P < 0.05). A higher incidence of first-dose and discharge medication was observed in patients with four drug coadministration during hospitalization than in patients with outpatient follow-up. The incidence of angiotensin-converting enzyme inhibitors (dry cough) was higher and the incidence of diuretics (hypokalemia) was lower in patients during hospitalization compared with patients at outpatient follow-up (P < 0.05). Maximum systolic blood pressure and fluctuations in systolic and diastolic blood pressure were lower in well compliant patients than in poorly compliant patients (P < 0.05). First systolic, maximal systolic, first diastolic, maximal diastolic, systolic and diastolic fluctuations were higher in hospitalised patients than in patients with outpatient follow-up, regardless of treatment compliance (P < 0.05). Conclusion: Elderly hypertensive patients with outpatient follow-up had the best discharge medication compliance, patients during hospitalization showed good medication compliance, and patients with outpatient follow-up had poor medication compliance.

Association Between High-Sensitivity C-Reactive Protein and Prognosis of Patients with Acute Cerebral Infarction.

Purpose: To investigate the association of serum high-sensitivity C-reactive protein (hs-CRP) with the severity of neurological deficits and prognosis in patients with acute cerebral infarction (ACI). Patients and Methods: In this retrospective analysis, 119 patients with ACI were recruited from January to December 2020. The serum hs-CRP level was measured by a latex-enhanced immunoturbidimetric assay. The severity of neurological deficits and prognosis of ACI patients were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Multivariate logistic analysis was performed and receiver operating characteristic (ROC) curves were plotted to evaluate the value of hs-CRP in predicting the prognosis of ACI. Results: The patients with a more favorable prognosis (mRS score 0-2) had a lower median serum hs-CRP level than those with a worse prognosis (mRS score 3-6) (3.32 IQR: 1.51, 8.04 to 17.93 IQR:16.02, 19.01; P<0.001). After adjusting for potential confounders, multivariable linear regression showed that serum hs-CRP level was independently associated with NIHSS score (Beta = 0.952, P<0.001) and mRS score (Beta=0.878, P<0.001). Multivariate logistic analysis revealed that high hs-CRP level was an independent predictor of the poor prognosis in patients with ACI (adjusted1 OR = 1.995; 95% CI = 1.499-2.655; adjusted2 OR = 2.75; 95% CI = 1.015-7.457). ROC curve analysis indicated that the area under the curve for hs-CRP to predict poor prognosis was 0.986. The cutoff value, sensitivity, and specificity were 11.835 mg/L, 95%, and 92.5%, respectively. In terms of ischemic stroke subtypes, the serum hs-CRP level was higher in large-artery atherosclerosis (LAA) patients than in those with small-artery occlusion (SAO) and cardioembolism (CE). In addition, the patients with LAA had higher scores of NIHSS and mRS than those with SAO and CE. Conclusion: Serum hs-CRP level is an independent predictor of prognosis, and an efficient index to discriminate patients with ACI, especially for those with LAA.

A Prediction Model of the Incidence of Nonalcoholic Fatty Liver Disease With Visceral Fatty Obesity: A General Population-Based Study.

Objective: This study aimed to distinguish the risk variables of nonalcoholic fatty liver disease (NAFLD) and to construct a prediction model of NAFLD in visceral fat obesity in Japanese adults. Methods: This study is a historical cohort study that included 1,516 individuals with visceral obesity. All individuals were randomly divided into training group and validation group at 70% (n = 1,061) and 30% (n = 455), respectively. The LASSO method and multivariate regression analysis were performed for selecting risk factors in the training group. Then, overlapping features were selected to screen the effective and suitable risk variables for NAFLD with visceral fatty obesity, and a nomogram incorporating the selected risk factors in the training group was constructed. Then, we used the C-index, calibration plot, decision curve analysis, and cumulative hazard analysis to test the discrimination, calibration, and clinical meaning of the nomogram. At last, internal validation was used in the validation group. Results: We contract a nomogram and validated it using easily available and cost-effective parameters to predict the incidence of NAFLD in participants with visceral fatty obesity, including ALT, HbA1c, body weight, FPG, and TG. In training cohort, the area under the ROC was 0.863, with 95% CI: 0.84-0.885. In validation cohort, C-index was 0.887, with 95%CI: 0.857-0.888. The decision curve analysis showed that the model's prediction is more effective. Decision curve analysis of the training cohort and validation cohort showed that the predictive model was more effective in predicting the risk of NAFLD in Japanese patients with visceral fatty obesity. To help researchers and clinicians better use the nomogram, our online version can be accessed at https://xy2yyjzyxk.shinyapps.io/NAFLD/. Conclusions: Most patients with visceral fatty obesity have a risk of NALFD, but some will not develop into it. The presented nomogram can accurately identify these patients at high risk.

[Analysis of clinical characteristics and prognosis of 4 264 patients with asymptomatic and mild novel coronavirus infections in Shanghai].

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment. METHODS: Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed. RESULTS: A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37:1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). CONCLUSIONS: The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.