Clinical features and risk factors associated with severe COVID-19 patients in China / 中华医学杂志(英文版)

BACKGROUND@#Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines.@*METHODS@#A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19.@*RESULTS@#A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004).@*CONCLUSIONS@#The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

Curcumin Inhibits Lipopolysaccharide-Induced Mucin 5AC Hypersecretion and Airway Inflammation via Nuclear Factor Erythroid 2-Related Factor 2 / 中华医学杂志(英文版)

<p><b>Background</b>Excess mucus production is an important pathophysiological feature of chronic inflammatory airway diseases. Effective therapies are currently lacking. The aim of the study was to evaluate the effects of curcumin (CUR) on lipopolysaccharide (LPS)-induced mucus secretion and inflammation, and explored the underlying mechanism in vivo and in vitro.</p><p><b>Methods</b>For the in vitro study, human bronchial epithelial (NCI-H292) cells were pretreated with CUR or vehicle for 30 min, and then exposed to LPS for 24 h. Next, nuclear factor erythroid 2-related factor 2 (Nrf2) was knocked down with Nrf2 small interfering RNA (siRNA) to confirm the specific role of Nrf2 in mucin regulation of CUR in NCI-H292 cells. In vivo, C57BL/6 mice were randomly assigned to three groups (n = 7 for each group): control group, LPS group, and LPS + CUR group. Mice in LPS and LPS + CUR group were injected with saline or CUR (50 mg/kg) intraperitoneally 2 h before intratracheal instillation with LPS (100 μg/ml) for 7 days. Cell lysate and lung tissue were obtained to measured Mucin 5AC (MUC5AC) and Nrf2 mRNA and protein expression by a real-time polymerase chain reaction and Western blotting. Bronchoalveolar lavage fluid (BALF) was collected to enumerate total cells and neutrophils. Histopathological changes of the lung were observed. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared.</p><p><b>Results</b>CUR significantly decreased the expression of MUC5AC mRNA and protein in NCI-H292 cells exposed to LPS. This effect was dose dependent (2.424 ± 0.318 vs. 7.169 ± 1.785, t = 4.534, and 1.060 ± 0.197 vs. 2.340 ± 0.209, t = 7.716; both P < 0.05, respectively) and accompanied by increased mRNA and protein expression of Nrf2 (1.952 ± 0.340 vs. 1.142 ± 0.176, t = -3.661, and 2.010 ± 0.209 vs. 1.089 ± 0.132, t = -6.453; both P < 0.05, respectively). Furthermore, knockdown of Nrf2 with siRNA increased MUC5AC mRNA expression by 47.7%, compared with levels observed in the siRNA-negative group (6.845 ± 1.478 vs. 3.391 ± 0.517, t = -3.821, P < 0.05). Knockdown of Nrf2 with siRNA also markedly increased MUC5AC protein expression in NCI-H292 cells. CUR also significantly decreased LPS-induced mRNA and protein expression of MUC5AC in mouse lung (1.672 ± 0.721 vs. 5.961 ± 2.452, t = 2.906, and 0.480 ± 0.191 vs. 2.290 ± 0.834, t = 3.665, respectively; both P < 0.05). Alcian blue/periodic acid-Schiff staining also showed that CUR suppressed mucin production. Compared with the LPS group, the numbers of inflammatory cells (247 ± 30 vs. 334 ± 24, t = 3.901, P < 0.05) and neutrophils (185 ± 22 vs. 246 ± 20, t = 3.566, P < 0.05) in BALF decreased in the LPS + CUR group, as well as reduced inflammatory cell infiltration in lung tissue.</p><p><b>Conclusion</b>CUR inhibits LPS-induced airway mucus hypersecretion and inflammation through activation of Nrf2 possibly.</p>

Effect of chronic intermittent hypoxia on theophylline metabolism in mouse liver / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver, which is the most important organ for drug metabolism. This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.</p><p><b>METHODS</b>Eight C57BL/6J mice were exposed to CIH for 12 weeks. Eight C57BL/6J mice were exposed to room air as a control group. Serum levels of alanine aminotransferase and aspartate aminotransferase were measured. Liver histology was observed by light and electron microscopy. Total hepatic cytochrome P450 concentration was measured. Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours. After incubation, the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.</p><p><b>RESULTS</b>CIH did not affect the serum transaminase levels. Livers from mice exposed to CIH showed hepatocellular edema, and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope. The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60 ± 2.43)% vs. (21.58 ± 4.52)% (P = 0.02). The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group; (0.83 ± 0.08) vs. (1.13 ± 0.21) mol/mg microsomal protein (P = 0.004).</p><p><b>CONCLUSION</b>CIH decreases theophylline metabolism by mouse hepatocytes, which may correlate with the downregulation of cytochrome P450 expression by CIH.</p>

Correlation between the incidence of hip fractures and the proximal femur by 3D geometric anatomy / 医用生物力学

Objective To measure the hip anatomic parameters and explore the differences between the hip fracture group and the normal group, analyze their effect on the incidence of hip fractures and fracture types by using computer aided design (CAD) and three-dimensional reconstruction technique. Methods Through CT scan images from the lower-extremity of hip fracture patient, the 3D anatomic model was established by Mimics10.01 software, and the 3D anatomic parameters of the normal proximal femur, namely femoral neck anteversion angle (FNAA), neck-shaft angle (NSA), femoral head diameter (FHD), length of femoral neck axis (LFNA) in the lower-extremity were measured. Results The averages of FNAA, NSA, FHD, LFNA in femoral neck fracture group were (7.9±4.6)°, (128.6±4.6)°, (46.0±4.6) mm, (47.1±5.1) mm, and those parameters in intertrochanteric fracture group were (15.5±6.8)°, (134.7±6.9)°, (45.3±3.6) mm, (46.7±3.4) mm. The FNAA and NSA in intertrochanteric fracture group were significantly larger than those in femoral neck fracture group regardless of gender (P<0.01). The FNAA and NSA in both fracture groups showed significant differences as compared with the normal group. ConclusionsThe risk of femoral intertrochanteric fracture will increase when the FNAA is larger than the normal range in Chinese, while the risk of femoral neck fracture will increase when the FNAA is smaller than the normal range in Chinese. The NSA of hip fracture patients was larger as compared with normal Chinese. The larger NSA will lead to a higher risk of femoral intertrochanteric fracture. There exist some differences in anatomic parameters of the proximal femur between the fracture group and the normal group, especially in the angle parameter. The femoral intertrochanteric fractures are more prone to occur in the older people, while the femoral neck fractures are more prone to occur in the younger people.

Effects of sex and lower extremity alignment on orientation of the knee joint line in knee surgery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Determination of the proper orientation of the knee articular surface is required both for correction of knee malalignment by osteotomy and for correct component alignment in knee arthroplasty. We sought to determine whether the patients' sex and lower extremity alignment (hip-knee-ankle angle) affects proper knee realignment in osteotomy or component alignment in total knee arthroplasty.</p><p><b>METHODS</b>We examined 199 healthy adult knees with malalignment of < 5° to determine the mechanical medial distal femoral angle, mechanical medial proximal tibial angle, surgical transepicondylar axis angle, and discrepancies between bone-cut orientations of osteotomy or total knee arthroplasty and the joint line of the distal femoral condyles, posterior femoral condyles and proximal tibial plateaus, using a three-dimensional computed tomography model.</p><p><b>RESULTS</b>The mean mechanical medial distal femoral angle and mean mechanical medial proximal tibial angle were (94.4 ± 1.9)° and (87.6 ± 1.8)° respectively for women and (93.8 ± 2.0)° and (87.1 ± 1.4)° respectively for men. The surgical transepicondylar axis angle was (2.9 ± 1.6)° for women and (3.2 ± 1.7)° for men. Independent of sex, the hip-knee-ankle angle was closely related to the mechanical medial distal femoral angle and mechanical medial proximal tibial angle, but not to the surgical transepicondylar axis angle. A slightly more valgus alignment of the knee and a more valgus angulation of the distal femoral joint line were found in women, whereas a more varus angulation of the proximal tibial joint line was found in men. Sex had the greatest effect on knee joint line orientation when the lower extremity was valgus in alignment.</p><p><b>CONCLUSIONS</b>A more valgus femoral joint line can be expected in women and in persons with valgus lower extremity alignment; a more varus tibial joint line can be found in men and in persons with varus lower extremity alignment.</p>

New variables for measuring joint space width to evaluate knee osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Assessing the radiographic features of knee osteoarthritis (OA), especially joint space narrowing, is important for evaluating disease progression. The purpose of this study was to quantitatively analyze joint space narrowing by measuring 2 new variables: the average joint space width (aJSW) and the articulate angle (AA) on X-ray films, and to evaluate the relationship between the 2 variables, knee function and OA symptoms.</p><p><b>METHODS</b>Using the web-based radiology viewer (Cedara I-Reach™ 4.1.1), we measured the 2 variables in 50 knees of 41 patients with knee OA participating in the Shanghai OA Study. We also evaluated the Kellgren-Lawrence (K-L) grade, the Western Ontario and McMaster Universities OA Index (WOMAC), and additional questionnaire in OA knees. The study was approved by the ethics committee of Shanghai Ninth People's Hospital (No. 2009 - 28).</p><p><b>RESULTS</b>The aJSW correlated with the K-L grade (r = -0.57, P < 0.001), kneeling (r = -0.29, P = 0.04), sitting cross-legged on the floor (r = -0.31, P = 0.03), WOMAC pain (r = -0.31, P = 0.03), WOMAC disability (r = -0.35, P = 0.01), pain while squatting (r = -0.37, P = 0.01), and defecating in a squatting position (r = -0.39, P = 0.01). The AA correlated with defecating in a squatting position (r = 0.29, P = 0.05), WOMAC disability (r = 0.30, P = 0.04) and K-L grade (r = 0.44, P = 0.003). The K-L grade also correlated with pain while squatting (r = -0.40, P = 0.005) and defecating in a squatting position (r = -0.34, P = 0.02), WOMAC pain (r = 0.30, P = 0.04), and WOMAC disability (r = 0.30, P = 0.04).</p><p><b>CONCLUSIONS</b>The aJSW closely correlated with knee OA symptoms and function scores, and was more sensitive to knee OA related disabilities than K-L grade and the AA. The aJSW could be used as a new variable for knee OA evaluation.</p>

Intermittent hypoxia and isoniazid plus rifampicin affect hepatic ultrastructure in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic intermittent hypoxia is the most important pathophysiologic feature of sleep apnea syndrome. The present study aimed to determine whether chronic intermittent hypoxia, which is associated with sleep apnea syndrome, can cause or increase damage to liver cell ultrastructure induced by isoniazid and rifampicin in mice.</p><p><b>METHODS</b>Based on a 2 × 2 full factorial design consisting of two factors of chronic intermittent hypoxia and isoniazid plus rifampicin, 32 male C57B6J mice were randomized into the control group, the chronic intermittent hypoxia group, the isoniazid plus rifampicin group, and the chronic intermittent hypoxia + isoniazid plus rifampicin group. Twelve weeks after treatment, we examined the ultrastructure of liver cells and quantitatively analyzed mitochondrial morphology in C57B6J mice.</p><p><b>RESULTS</b>Chronic intermittent hypoxia did not significantly affect the ultrastructure of liver cells. The main effect of chronic intermittent hypoxia did not lead to an increase of mean profile area or mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P > 0.05). Isoniazid plus rifampicin significantly affected liver cell ultrastructure. The main effect of isoniazid plus rifampicin resulted in an increase of mean profile area and mean perimeter of mitochondria, and a decrease of numerical density on area of mitochondria (all P < 0.05). Moreover, there was a positive interaction among the chronic intermittent hypoxia and the isoniazid plus rifampicin groups for mean profile area, mean perimeter, and numerical density on area of mitochondria (all P < 0.05).</p><p><b>CONCLUSION</b>Chronic intermittent hypoxia and isoniazid plus rifampicin treatment lead to synergistic liver cell ultrastructural injury.</p>

Effect of chronic intermittent hypoxia on the expression of Nip3, cell apoptosis, beta-amyloid protein deposit in mice brain cortex / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic intermittent hypoxia (CIH) is the most important pathophysiologic feature of sleep apnea syndrome (SAS). To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis and beta-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study.</p><p><b>METHODS</b>Thirty male ICR mice were divided into four groups: control group (A, n = 10, sham hypoxia/reoxygenation), 2 weeks CIH group (B, n = 5), 4 weeks CIH group (C, n = 5), and 8 weeks CIH group (D, n = 10). The ICR mice were placed in a chamber and exposed to intermittent hypoxia (oxygen concentration changed periodically from (21.72 +/- 0.55)% to (6.84 +/- 0.47)% every two minutes, eight hours per day). Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling (TUNEL). Immunohistochemical staining was performed for measuring expression of Nip3 and beta-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.</p><p><b>RESULTS</b>TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Ri into group A (1, 5.5), group B (133, 13), group C (252, 21), and group D (318, 24). There were significant differences among the above four groups (P = 0.000). The significance test was performed between the control group and each CIH group respectively: group A and B (P > 0.05); group A and C (P < 0.01); and group A and D (P < 0.005). The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows: group A (2, 5.5), group B (117, 13), group C (227, 26.2), and group D (479, 21.4). There were significant differences among the four groups (P = 0.000). The statistical test was performed between the control group and each CIH group respectively: groups A and B (P > 0.05); groups A and C (P < 0.005); and groups A and D (P < 0.005). There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain (P < 0.05). The expression of beta-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of neural sheath in all CIH groups but not in the control group.</p><p><b>CONCLUSION</b>The results of this study indicate that CIH could up-regulate the expression of Nip3, and result in neuron apoptosis and ultrastructural changes in neurons of the frontal cortex.</p>