Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Objective To establish a health education program for home emergency management of acute complications of diabetes in the elderly.Methods The program was drafted by literature review and panel discussion.The final draft was formed after two rounds of correspondence from 13 experts.Results The recovery rate of the two rounds of expert correspondence was 100%,and the expert authority coefficient was 0.98.The Kendall's harmony coefficients of the two rounds of correspondence were 0.263 and 0.212 respectively(both P<0.001).The established health education program included indicators of three categories:early stage of acute complications of diabetes at home(understanding the inducing factors),emergency warning(quick and early identification in case of emergency),and emergency treatment at home.Conclusion The contents of the health education program are systematic and reliable and meet the needs of health education for home emergency management of the elderly with diabetes.
Humans ; Aged ; Delphi Technique ; Health Education ; Diabetes Mellitus/therapy* ; Diabetes Complications

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).
Antioxidants/chemistry* ; Tandem Mass Spectrometry/methods* ; Prunella/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Caffeic Acids ; Flavonoids/analysis* ; Triterpenes/analysis* ; Saponins ; Sugars

OBJECTIVE: To evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19). METHODS: This multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate. RESULTS: A total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5-17], the median hospitalization duration was 15 d (IQR 12-20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2-6), 8 d (IQR 5-12), and 8 d (IQR 5-11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10-17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment. CONCLUSION BDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836).
C-Reactive Protein ; China ; Cough/drug therapy* ; Disease Progression ; Fatigue ; Fever ; Humans ; Nucleic Acids ; Oxygen ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; COVID-19 Drug Treatment

Objective To evaluate the risk of hearing loss of assembly workers in an automobile manufacturing factory. Methods An 8-hour equivalent sound level monitoring was carried out for assembly posts in an automobile factory. The risk of noise-induced hearing loss of assembly workers was measured using the method specified in ISO 1999:2013(E). The risk of noise-induced hearing loss was assessed in a graded manner according to the Guidelines for the Management of Occupational Disease Hazards from Noise. The results were statistically analyzed using Pearson correlation analysis. Results The average 8-hour equivalent sound level of the assembly work post in this automobile manufacturing factory was 89.5 dB (A). At 4000 Hz, the hearing loss N₅₀ (dB) of assembly workers reached the maximum. The longer the exposure time, the higher the risk of high-frequency standard hearing threshold shift. The risk of high-frequency standard hearing threshold shift was at a relatively high level at 30 years of work, while the risk of noise deafness reached a higher level after 40 years of work. Conclusion The 8-hour equivalent sound level (L_EX,8h) of assembly workers in the automobile factory exceeds the occupational exposure limit. With the increase of exposure years, the risk of high-frequency standard hearing threshold shift and noise deafness increases.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

Abstract: Objective To analyze the effect of nutrition package on the nutritional status and prevalence of children in rural areas of Hainan Province, and provide scientific basis and suggestions for further improving the nutritional and health status of children in this region. Methods　Four cities and counties were randomly selected as the intervention group, and four cities and counties matched with the intervention group in terms of population, economy, social culture, maternal and child health work foundation of township health centers, physical nutrition and health status were selected as the control group.With the combination of monitoring and prospective cohort study, infants in the intervention group and the control group were studied from June 1, 2020, and they were intervened for 12 months with supplementary food nutrition package. Before and after intervention, the nutrition and health status of infants aged 6-24 months in the intervention group and the control group were investigated to evaluate the nutritional and health effects of supplementary food nutrition package for infants aged 6-24 months in rural Hainan Province. Results　A total of 999 infants were investigated, including 427 in the intervention group and 572 in the control group. After 12 months of nutritional intervention, there was no significant difference in weight-for-age Z-score (WAZ) and height-for-age Z-score (HAZ) and weight-for-height Z-score (WHZ) between the intervention group and the control group (P>0.05). The rate of emaciation of the intervention group was 1.64%, which was significantly lower than 3.67% of the control group (P<0.05). There were no significant differences in the rate of growth retardation (2.81% and 3.32%, respectively) and underweight (0.47% and 1.92%, respectively) between the intervention group and the control group (P>0.05). The rate of respiratory infection and diarrhea in the intervention group were 9.13% and 1.17%, which were significantly lower than corresponding 23.25% and 3.15% in the control group (P<0.05). The hemoglobin of the intervention group and the control group were 117.24 g/L and 114.51 g/L respectively, and the rates of anemia were 11.11% and 22.84% respectively, the differences were statistically significant (P<0.05). Conclusions　The intervention of nutrition package in rural areas of Hainan Province has achieved the expected results, and supplementary food nutrition package has reduced the incidence of malnutrition and respiratory infection and diarrhea in recent two weeks in infants and anemia to a certain extent. We should attach great importance to the supplementary nutrition package for right-age children and promote the growth and health of children in rural areas through supplementary nutrition package, and continuously improve the nutrition and health level of children in Hainan Province.

Objective: To develope and validate a reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of vardenafil concentration in plasma of rat. Methods: Plasma samples of normal Sprague-Dawley rats were collected. A Phenomenex Synergi Polar-RP 80A column (2.0 mm×50 mm, 4 µm) was used. Column temperature was set at 30 ℃. Mobile phase A was 0.1% formic acid in water; mobile phase B was 0.1% formic acid in acetonitrile. The flow rate was 0.4 ml/minutes. Quantitative determination was performed by electrospray ionization, operating in positive ion multiple reaction monitoring (MRM) mode. Cisapride was used as the internal standard. The feasibility of the method was evaluated by examining its specificity, linearity and quantitative range, precision and accuracy, matrix effects, and stability. Results: Under the selected chromatographic and mass spectrometry conditions, the monitoring ions of vardenafil and internal standard were mass-to-charge ratio（m/z) 489.3/151.2 and 466.4/234.2, the retention times of vardenafil and internal standard were 2.62 and 2.80 minutes, respectively, and the peak shape was satisfactory. The method has good linearity in the concentration range of 0.2-200 ng/ml. The intra-batch precision (%CV) and accuracy (%DEV) of vardenafil were 1.5%-9.7% and -6.8%-6.6%, respectively. The inter-batch precision and accuracy of vardenafil were 3.1% -8.4% and -3.7%-4.6%, respectively. In this sample processing method, the extraction recovery rate of vardenafil was obtained at range of 88.2%-104.6%, which met the requirements for the investigation of extraction recovery rate. In this sample processing method, the normalized matrix factor of each quality control concentration of vardenafil was 1.04, 0.85, and 1.04, and the coefficient of variation (%CV) was in the range of 1.7%-10.7%, which met the requirements for the investigation of matrix effects. Variations of short-term stability, long-term stability, and stability of 4 freeze-thaw cycles of vardenafil was within ±15%, and the coefficient of variation were within 5%. Conclusion: The high performance liquid chromatography-tandem mass spectrometry method established in this study is feasible for the measurement of concentration of vardenafil in rat plasma and this method has good specificity and high accuracy, and can be used to detect the concentration of vardenafil in rat plasma.
Animals ; Chromatography, Liquid ; Feasibility Studies ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; Vardenafil Dihydrochloride