ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug， and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine， namely Qizhi Tongluo capsules， and the key technical framework of precise clinical positioning of Chinese patent medicine， which was manifested as a comparison of prescription target spectral effect， discovery of core value of prescription， and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial， based on the multi-component， multi-target， and multi-phenotype data of prescription and clinical indication， the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then， based on the predicted clinical advantages， reasonable efficacy indicators were selected， and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Objective:To evaluate the role of cold-inducible RNA-binding protein (CIRP) in acute renal injury in a mouse model of myocardial ischemia-reperfusion (I/R) and the relationship with nuclear factor kappa B (NF-κB) signaling pathway.Methods:Twenty-four SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, with body mass index of 24-28 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group) and myocardial I/R + CIRP-derived peptide C23 group (I/R+ C23 group). The model of myocardial I/R was developed by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. CIRP-derived peptide C23 8 mg/kg was intraperitoneally injected before myocardial ischemia and reperfusion in I/R+ C23 group, while Sham group was only threaded without ligation. Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB), lactic dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) concentrations. Renal tissues were obtained for examination of the pathological changes, and the tubular injury score was assessed. The expression of NF-κB, phosphorylated NF-κB (p-NF-κB), Nod-like receptor protein 3 (NLRP3), interleukin-1beta (IL-1β) and IL-18 in renal tissues was detected by Western blot. The expression of Toll-like receptor 4 (TLR4), NLRP3, IL-1β, TNF-α and IL-6 mRNA was determined by real-time polymerase chain reaction. Results:Compared with Sham group, the levels of serum CK-MB, LDH, Cr and BUN and renal tubule injury score were significantly increased, the expression of p-NF-κB, NLRP3, IL-1β and IL-18 was up-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and the pathological injury to renal tissues was aggravated in I/R group. Compared with I/R group, the serum CK-MB, LDH, Cr, BUN and renal tubular injury score were significantly decreased, and the expression of p-NF-κB, NLRP3, IL-1β and and IL-18 was down-regulated, the expression of TLR4, NLRP3, IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the pathological injury to renal tissues was alleviated in I/R+ C23 group. Conclusions:CIRP is involved in the process of acute renal injury in a mouse model of myocardial I/R, which is associated with activation of NF-κB signaling pathway and promotion of inflammatory responses.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.
COVID-19 ; Cohort Studies ; Hepatitis B, Chronic/epidemiology* ; Humans ; Retrospective Studies ; Risk Factors

Objective:To explore the value of proton density fat fraction(PDFF) based on histogram analysis for quantification hepatic steatosis and fibrosis in rabbit model and the interference of hepatic fibrosis to the evaluation of hepatic steatosis with PDFF.Methods:From March to November 2020, 135 New Zealand white rabbits were randomly divided into control group ( n=30) and experimental group ( n=105) using a random number table. The volume ratio of CCl 4 and olive oil was 1∶1 to prepare 50% CCl 4 oil solution, and experimental rabbits were subcutaneously injected with the oil solution. An equal dose of normal saline was subcutaneously injected for control group rabbits. At the end of the 4 th, 8 th, and 12 th week, 35 in the experimental group and 10 rabbits in the control group were randomly selected to conduct the mDixon-Quant scanning, and histogram analysis of PDFF was analyzed including volume, mean, median, standard deviation, 25 th, 50 th, 75 th, 90 th quantile, skewness, kurtosis, entropy and inhomogeneity. After the examination, the rabbits were sacrificed and the liver percentage of steatosis (PSH) and fibrosis (POF) were recorded by semi-quantitative analysis. Spearman correlation analysis was used to correlate PDFF with PSH and POF. Multiple linear regression analysis was used to determine independent PDFF histogram parameters for evaluating PSH and POF. A receiver operator characteristic (ROC) curve was used to assess the diagnostic accuracy of PDFF for discriminating mild from moderate-severe hepatic steatosis and mild from moderate-severe hepatic fibrosis with median of PSH or POF for dichotomy, and DeLong test was used to compare the area under the curve (AUC). With the correction of hepatic fibrosis, correlation coefficient and AUC were compared of PDFF for discrimination mild from moderate-severe hepatic steatosis. Results:The PDFF mean, median, standard deviation, 75 th, 90 th showed correlation with PSH ( r=0.558, 0.522, 0.319, 0.723, 0.646, -0.589, all P<0.05). The entropy and 75 th were independent parameters for evaluating PSH (β=2.347, -5.960, P=0.018, 0.001). The PDFF 75 th was the optimal parameter for discriminating mild from moderate-severe hepatic steatosis with AUC=0.915 ( P=0.001). The PDFF volume, mean, median, standard deviation, 75 th, 90 th, entropy showed correlation with POF ( r=0.355, 0.393, 0.376, 0.298, 0.485, 0.426, -0.681, all P<0.05). The entropy, standard deviation and volume (β=-11.041, 1.356, 0.190, P=0.001, 0.026, 0.016) were independent parameters for evaluation of hepatic fibrosis, and the entropy was the optimal parameter for hepatic fibrosis (AUC=0.771, P=0.001). The correlation between PSH and PDFF 75 th was less pronounced when fibrosis was present ( r=0.512, P=0.001) than when fibrosis was absent ( r=0.751, P=0.002). The PDFF 75 th showed a significant difference in discriminating mild hepatic steatosis from moderate-severe hepatic steatosis after correction of POF (AUC=0.895, 0.950, Z=2.970, P=0.025). Conclusions:PDFF based on histogram analysis provided a noninvasive, accurate estimation of quantification for hepatic steatosis and fibrosis. Hepatic fibrosis reduced the correlation between hepatic steatosis and PDFF and the presence of hepatic fibrosis can confound the quantification of hepatic steatosis with PDFF.

Objective: To investigate the reversibility of ischemic core defined by CT perfusion imaging in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis within different time windows and influencing factors. Methods: The data of AIS patients who received intravenous thrombolysis in the Department of Neurology of Lishui People′s Hospital from May 2016 to December 2018 were retrospectively reviewed. All patients had finished multi-model CT imaging before thrombolysis and multi-model MRI examination 24-48 hours after thrombolysis. The baseline ischemic core volume (hypoperfusion area with relative cerebral blood flow (rCBF)<30%) was quantitatively assessed based on CT perfusion images using MIStar software, and the final ischemic core volume was assessed based on diffusion weighted imaging acquired 24-48 hours after thrombolysis. The reversibility of ischemic core was defined as baseline ischemic core volume-the final infarct volume ≥5 ml. Then the clinical and imaging features of the patients between reversible group and irreversible group were compared, and the predictors of ischemic core reversibility were analyzed by binary Logistic regression analysis. Results: Finally, 97 patients were enrolled in the present study, of which 64 (66%) patients achieved successful recanalization, 51 (53%) patients with reversible baseline ischemic core. For patients with recanalization, the incidence of reversibility was 76% (26/34), 71% (17/24), 2/5 and 0 (0/1) in patients with time window from onset to thrombolysis (ONT) <3.0 h, 3.0-4.5 h, 4.6-6.0 h, and >6.0 h, respectively. In the non-recanalization group, six patients were also showed with ischemic core reversibility, including 4 (4/12) in the ONT<3.0 h group and 2 (2/12) in the ONT 3.0-4.5 h group. It was found that the reversible volume was positively correlated with baseline ischemic core volume (r=0.805, P<0.001) by Spearman correlation analysis. Finally, binary Logistic regression analysis revealed that the history of hypertension, ONT and recanalization were independent predictors of reversible changes of baseline ischemic core. Conclusions The ischemic core defined by CT perfusion imaging (rCBF<30%) was considerably inaccurate for patients with ONT<6.0 h. If recanalization could be achieved within this time window, most of the patients would manifest with ischemic core reversibility, the predictors of which also included hypertension history and ONT.