Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Effects of bronchial thermoplasty and cryoablation on airway smooth muscle / 中华医学杂志(英文版)

BACKGROUND@#The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM).@*METHODS@#Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups.@*RESULTS@#In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ± 7.75 μm vs. 17.57 ± 15.20 μm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ± 11.02 μm), BT group and CBA group (13.41 ± 4.40 μm and 4.81 ± 4.44 μm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ± 4.42 μm vs. 7.41 ± 7.20 μm, P = 0.540). Compared with the control group (0.161 ± 0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ± 0.022, 0.072 ± 0.012, 0.074 ± 0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613).@*CONCLUSIONS@#CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.

Distribution of HoxA13 in the prepuce and urethral plate in different types of hypospadias and its implication / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role of the HoxA13 gene from the HOX family in the development of hypospadias by detecting the transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients.</p><p><b>METHODS</b>We collected the tissues from the prepuce and urethral plate of 30 hypospadias patients aged 3.3 - 11.6 years, the prepuce of 10 phimosis children aged 3.1 - 10.4 years and the urethra of 10 penile carcinoma patients aged 48.1 - 75.6 years with no urethral involvement, the latter 20 taken as controls. We divided the tissue samples into a distal, an intermedial, a proximal and a control group, and detected the expressions of HoxA13 mRNA and protein in different groups by RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>RT-PCR showed that the HoxA13 mRNA expressions in the prepuce and urethral plate were significantly higher in the control group (1.409 +/- 0.441 and 1.270 +/- 0.209) than in the intermedial (0.848 +/- 0.338 and 0.684 +/- 0.228) and proximal group (0.497 +/- 0.218 and 0.464 +/- 0.164) (P < 0.05 or P < 0.01), and so were they in the distal (1.071 +/- 0.342 and 1.054 +/- 0.189) than in the proximal group (P < 0.05). Immunohistochemistry revealed that the HoxA13 protein expressions in the prepuce and urethral plate were remarkably higher in the control group (12 050 +/- 4 112 and 13 420 +/- 2 636) than in the intermedial (5 217 +/- 1 993 and 5 238 +/- 3 065) and proximal group (2 095 +/- 1 591 and 2 238 +/- 2 217) (P < 0.05 or P < 0.01), and so were they in the distal (8 223 +/- 3 212 and 10 450 +/- 2 123) than in the proximal group (P < 0.05).</p><p><b>CONCLUSION</b>The transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients are closely related with the abnormal position of the urethral meatus, and their abnormal expressions may affect the development and formation of the urethra.</p>

Microwave induces apoptosis in A549 human lung carcinoma cell line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Microwaves have other biological effects on cancer as well besides killing tumor cells by coagulation. Some studies showed that microwaves may induce apoptosis in some tumor cells. The apoptotic effect of microwaves may help in clinic to remove residual malignant cells nearby the primary lesion and avoid relapse subsequently. However, there is little evidence on this subject from lung cancer. We studied the effect of microwaves on inducing apoptosis in the human lung carcinoma cell line A549 cells, aiming to identify its effect on apoptosis.</p><p><b>METHODS</b>A549 cells were radiated by various intensities and durations of microwaves. Apoptosis induction in A549 cells was analyzed by morphological observations, tetrazolium blue color method (MTT) assays, flow cytometry, immunohistochemistry, and image analyses.</p><p><b>RESULTS</b>Morphological changes in A549 cells, including cell shrinking and nuclear pyknosis, were observed after microwave radiation. Microwaves significantly inhibited metabolic activities and induced apoptosis in A549 cells. The results of the MTT assay showed a significant decrease of cell activities in all the radiation groups compared with the normal control (P < 0.01). The low point of cell activities often appeared at 6 - 12 hours after radiation. Apoptosis was also confirmed by flow cytometry. The early stage apoptotic rate reached 6.10% - 17.98% and the advanced stage apoptotic rate + necrosis rate reached 8.04% - 44.06% at 6 hours after microwave irradiation, in contrast to 2.32% and 4.10% in the respective control groups. Down-regulation of Bcl-2 expression and up-regulation of p53 expression were observed by immunohistochemistry after radiation. In most treated groups, the down-regulation of Bcl-2 expression reached its lowest level at 3 - 6 hours after radiation (integrated optical density (IOD)-6 hours: 2.13 ± 0.08 - 5.14 ± 0.13 vs. control: 5.79 ± 0.10, P < 0.01) and the up-regulation of P53 expression peaked at about 3 hours (IOD-3 hours: 2.61 ± 0.13 - 8.07 ± 0.11 vs. control: 1.29 ± 0.07, P < 0.01). Cell damage, apoptosis, and protein expression levels in the samples differed depending on the radiation intensity and duration.</p><p><b>CONCLUSIONS</b>Microwaves can promote apoptosis in A549 cells. The effect depends on the duration and dosage of microwave radiation. Bcl-2 and p53 proteins may be involved in the apoptotic process of A549 cells induced by microwaves.</p>