OBJECTIVE To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control. METHODS The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities. RESULTS It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible. CONCLUSION Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.

In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.

In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.

ObjectiveTo explore the risk factors of stroke-associated pneumonia (SAP) for patients with mild to moderate acute ischemic stroke (AIS). MethodsFrom October, 2016 to December, 2019, 321 patients with mild to moderate AIS in Beijing Bo'ai Hospital were collected and divided into SAP group (n = 71) and non-SAP group (n = 250) according to whether they were complicated with SAP. Gender, age, time from symptom onset to admission, systolic pressure, diastolic pressure, scores of National Institutes of Health Stroke Scale (NIHSS) at admission, and medical history were recorded. Laboratory indexes including the count of white blood cell and platelet, levels of D-dimer, hypersensitive C-reactive protein (hs-CRP) and α-hydroxybutyrate dehydrogenase (α-HBDH) were measured. ResultsUnivariate analysis showed that age, NIHSS score, history of hypertension, atrial fibrillation, prior cerebral infarction, the count of white blood cell and platelet, the levels of D-dimer, hs-CRP and α-HBDH were the influencing factors of SAP (P < 0.2). Multivariate Logistic regression showed that age > 70 years old (OR = 7.121, 95%CI 3.493 to 14.514, P < 0.001), NIHSS score > 4 (5 to 10, OR = 4.861, 95% CI 2.412 to 9.797, P < 0.001), the count of platelet > 300×10⁹/L (OR = 6.978, 95% CI 1.864 to 26.128, P = 0.004), and the level of D-dimer > 1.0 mg/L (OR = 3.036, 95% CI, 1.518 to 6.071, P = 0.002) were the risk factors of SAP. The model fitted the original data well (HL = 1.509，P = 0.680) and appeared a good prediction (AUC = 0.847, 95% CI 0.796 to 0.898, P < 0.001). ConclusionAge > 70 years old, NIHSS score > 4 (5 to 10), the count of platelet > 300×10⁹/L and the level of D-dimer > 1.0 mg/L were the risk factors of SAP for patients with mild to moderate AIS.

Objective:To observe the changes of serum histone H4 level and its predictive value in patients with septic cardiomyopathy.Methods:A prospective study was conducted. A total of 147 patients with sepsis and septic shock were collected in emergency department. The general data were recorded. Transthoracic echocardiography and plasma histone H4 were conducted within 24 hours and 7 days after admission.The scores of sequential organ failure assessment(SOFA), acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 (NRS2002) were evaluated within 24 hours. According to whether septic cardiomyopathy occurred, the patients were divided into two groups, and dynamic changes of histone H4 on the first and seventh day of the two groups were observed. The factors influencing the occurrence of septic cardiomyopathy were analyzed by multivariate logistic regression. The prediction ability of serum histone H4 on septic cardiomyopathy was evaluated by receiver operating curve (ROC).Results:The incidence of septic cardiomyopathy was 28.6% (42 / 147). The level of histone H4 in septic cardiomyopathy group was higher than that in non septic cardiomyopathy group ( Z = 4.449, P < 0.001), and dynamic detection showed that the level of histone H4 on the seventh day was lower than that on admission ( Z=3.057, P=0.002). Multivariate logistic regression showed that the high serum histone H4 level [Odd Ratio( OR)=1.337, 95% confidence interval (95% CI) was 1.173-1.522, P < 0.001], SOFA ( OR= 1.474, 95% CI 1.227-1.769, P < 0.001), older age ( OR = 1.074, 95% CI 1.019-1.132, P = 0.008) were independent risk factors for septic cardiomyopathy. The area of ROC curve for serum histone H4 to predict septic cardiomyopathy was 0.729 ( P < 0.001), the predictive cut-off value was 10.81 ng/ml, which yielded a sensitivity 0.524 and a specificity of 0.914. Conclusions:The level of histone H4 showed dynamic change in septic cardiomyopathy, and high serum histone H4 level has a good predictive value for the occurrence of septic cardiomyopathy.

Objective:To investigate the relationship between sleep quality and slow-flow in patients with acute coronary syndrome during percutaneous coronary intervention(PCI) and its impact on clinical prognosis.Methods:200 patients with ACS hospitalized in the cardiology department of Guangzhou First People's Hospital from January 2017 to October 2018 were selected. The Pittsburgh Sleep Quality Index (PSQI) was measured before elective PCI, and the sleep breathing of patients was monitored by micro motion sensitive mattress sleep monitoring system (MSMSMS). The patients were divided into normal sleep group (68 cases, PSQI≤7 points) and sleep disorder group (132 cases, PSQI>7 points). The levels of plasma endothelin-1 (ET-1) and nitric oxide (NO) were measured. The " slow-flow" that took place during PCI were also recorded. Major cardiac adverse events (MACE) of patients took placed during 12 months follow-up periods were recorded and compared between two groups.Results:Compared with normal sleep group, patients in sleep disorder group had higher ratio of sleep apnea-hypopnea syndrome (SAHS), hypoxemia and lower deep sleep (25.00% vs 10.29%, 25.76% vs 11.76%, 66.67% vs 48.53%, all P<0.05); lower level of NO and higher level of ET-1 [(28.65±3.26)μmol/L vs (30.24±4.08)μmol/L; (21.17±3.08)pg/ml vs (18.90±2.95)pg/ml, P<0.05]; more slow-flow events took place during PCI in sleep disorder group than normal sleep group (16.67 vs 5.88%, P<0.05); After 12 months of follow-up, Kaplan-Meier survival analysis showed patients of the two groups had significantly different cumulative non-events survival rates (19.70% vs 7.35%, Log rank=5.06, P=0.025). Conclusions:Sleep disorder increase the slow-flow phenomenon during PCI in patients with ACS and affect the clinical prognosis.

Objective:To establish a clinical diagnostic scoring system for septic cardiomyopathy (SCM) and evaluate its diagnostic efficacy.Methods:A prospective cohort study was performed. Patients with sepsis and septic shock admitted to the department of emergency of China Rehabilitation Research Center were enrolled from January 2019 to December 2020. The baseline information, medical history, heart rate (HR), mean arterial pressure (MAP), body temperature and respiratory rate (RR) on admission were recorded. Laboratory indexes such as white blood cell count (WBC), hypersensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and blood lactic acid (Lac) were measured. Transthoracic echocardiography was conducted within 24 hours and on the 7th after admission. Sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluationⅡ(APACHEⅡ), and nutritional risk screening 2002 scale (NRS2002) were also assessed. The patients were divided into two groups according to whether SCM occurred or not. The risk factors of SCM were screened by univariate and multivariate Logistic regression. The cut-off value of continuous index was determined by receiver operator characteristic curve (ROC curve) and discretized concerning clinical data. The regression coefficient β was used to establish the corresponding score, and the clinical diagnostic score system of SCM was established. The diagnostic value of the model was evaluated by ROC curve.Results:In total, 147 patients were enrolled in the study and the incidence of SCM was 28.6% (42/147). Univariate Logistic regression analysis showed the risk factors of SCM included: ① continuous indicators: age, NT-proBNP, RR, MAP, Lac, NRS2002, SOFA, APACHEⅡ; ② discrete indicators: shock, use of vasoactive drugs, history of coronary heart disease, acute kidney injury (AKI). Multivariate Logistic regression analysis after discretization of above continuous index showed that age≥87 years old, NT-proBNP≥3 000 ng/L, RR≥30 times/min, Lac≥3 mmol/L and SOFA≥10 points were independent risk factors for SCM [age ≥87 years: odds ratio ( OR) = 3.491, 95% confidence interval (95% CI) was 1.371-8.893, P = 0.009; NT-proBNP≥3 000 ng/L: OR = 2.708, 95% CI was 1.093-6.711, P = 0.031; RR≥30 times/min: OR = 3.404, 95% CI was 1.356-8.541, P = 0.009; Lac≥3 mmol/L: OR = 3.572, 95% CI was 1.460-8.739, P = 0.005; SOFA≥10 points: OR = 8.693, 95% CI was 2.541-29.742, P = 0.001]. The clinical diagnostic score system of SCM was established successfully, which was composed of age≥87 years old (1 point), NT-proBNP ≥ 3 000 ng/L(1 point), RR≥30 times/min (1 point), Lac≥3.0 mmol/L (1 point), SOFA≥10 points (2 points), and the total score was 6 points. ROC curve analysis showed the cut-off value of the scoring system for diagnosing SCM was 3 points, the area under ROC curve (AUC) was 0.833, 95% CI was 0.755-0.910, P < 0.001, with the sensitivity of 71.4%, and specificity of 86.7%. Conclusion:The clinical diagnostic scoring system has good diagnostic efficacy for SCM and contributes to early identification of SCM for clinicians.

Objective To determine the impact of hypertension on the outcomes of patients with COVID-19. Methods This matched cohort study was conducted among a total 442 patients with COVID-19 admitted in Honghu People's Hospital and First Affiliated Hospital of Nanchang University between January 1 to March 18, 2020, including 61 patients with hypertension and 381 normotensive patients. To minimize the effects of the confounding factors including age, gender and other comorbidities, we excluded patients with comorbidities other than hypertension, and matched the patients with and without hypertension for age and gender at a 1:1 ratio. We analyzed the clinical characteristics, laboratory findings and clinical outcomes of in 32 matched pairs of patients with and without hypertension. Results Compared with the normotensive patients, COVID-19 patients with hypertension were more likely to develop bacterial infections (P=0.002) and had higher neutrophil counts (P=0.007), neutrophil/lymphocyte ratio (P=0.045), and lactate dehydrogenase levels (P=0.035). A greater proportion of patients had bilateral patchy opacities on chest CT (P=0.012) in the hypertension group than in the normotensive group. COVID-19 patients with hypertension group were more likely to receive antibiotics (P=0.035) and corticosteroid therapies (P=0.035). Conclusion Hypertension increases the risk of bacterial infection in patients with COVID-19. Hypertensive patients with COVID-19 have higher neutrophil counts and neutrophil/lymphocyte ratios and are more likely to require treatment with antibiotics. Hypertensive patients with COVID-19 should therefore take cautions to avoid bacterial infections.

Objective To determine the impact of hypertension on the outcomes of patients with COVID-19. Methods This matched cohort study was conducted among a total 442 patients with COVID-19 admitted in Honghu People's Hospital and First Affiliated Hospital of Nanchang University between January 1 to March 18, 2020, including 61 patients with hypertension and 381 normotensive patients. To minimize the effects of the confounding factors including age, gender and other comorbidities, we excluded patients with comorbidities other than hypertension, and matched the patients with and without hypertension for age and gender at a 1:1 ratio. We analyzed the clinical characteristics, laboratory findings and clinical outcomes of in 32 matched pairs of patients with and without hypertension. Results Compared with the normotensive patients, COVID-19 patients with hypertension were more likely to develop bacterial infections (P=0.002) and had higher neutrophil counts (P=0.007), neutrophil/lymphocyte ratio (P=0.045), and lactate dehydrogenase levels (P=0.035). A greater proportion of patients had bilateral patchy opacities on chest CT (P=0.012) in the hypertension group than in the normotensive group. COVID-19 patients with hypertension group were more likely to receive antibiotics (P=0.035) and corticosteroid therapies (P=0.035). Conclusion Hypertension increases the risk of bacterial infection in patients with COVID-19. Hypertensive patients with COVID-19 have higher neutrophil counts and neutrophil/lymphocyte ratios and are more likely to require treatment with antibiotics. Hypertensive patients with COVID-19 should therefore take cautions to avoid bacterial infections.

OBJECTIVE： To synthetize the synthesis of mitoxantrone and evaluate its quality. METHODS： Crude product of mitoxantrone was prepared by slow oxidation of 1，4，5，8-tetrahydro-anthraquinone with N-（2-hydroxyethyl） ethylenediamine in water bath at 50 ℃ for 2 h under argon protection and in dry air for 4 h. The crude product was crystallized by ethanol-n-hexane  （4 ∶ 1，V/V） mixture solution， which was cooled overnight and then washed by ethanol-n-hexane mixture for many times. The melting range， pH value of solution， ultraviolet-visible absorption spectrum， infrared structural characteristics， drying weight loss （water loss rate） and critical relative humidity （CRH） of the purified products （4 batches） were investigated. HPLC method was used to determine the contents of mitoxantrone. RESULTS： The mitoxantrone was prepared successfully， and synthetic yield of mitoxantrone was 34.3％； the melting point ranged from 159.1-163.6 ℃. The aqueous solution was alkaline （pH 7.63-9.54）； there was a maximum ultraviolet absorption peak at 235-245 nm； there was a maximum absorption peak of visible light at 590-600 nm； the infrared characteristics were consistent with those described of mitoxantrone in the 2015 edition of the Infrared Spectrum Collection of Drugs； water loss rate were －0.83％-2.36％； CRH value was 54.7％， and the average content of the product was 78.1％（n＝4） by HPLC method. CONCLUSIONS： The mitoxantrone is synthesized under mild， non-toxic and harmless experiment conditions. The synthesis step is simple， the cost is low and the yield is high. The quality of products meets the quality requirements.