Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Electrophysiological characteristics of the isolated muscle spindle in rats / 生理学报

The aim of this study was to observe the electrophysiological characteristics of the isolated rat muscle spindle. The muscle spindle was isolated from rat soleus and the afferent discharge of the isolated muscle spindle was recorded by air-gap technique. In the basic physiological salt solution, the spontaneous impulses of muscle spindle were at a lower level with irregular intervals. The mean frequency of afferents was (51.78 ± 25.63) impulses/1 000 s (n = 13). The muscle spindle afferents were significantly increased and maintained over time by the addition of certain amino acids during the observation. The number of the action potential recorded per 1 000 s was 200-1 000 [mean: (687.62 ± 312.56) impulses/1 000 s, n = 17]. In addition to the typical propagated action potential, a large number of abortive spikes were observed. The results indicate that the activities of isolated muscle spindles in rats can be well maintained by the addition of certain amino acids. The results initially establish and provide the possibility for further research conducted in isolated rat muscle spindles.

Decreased neurotrophin-3 expression of intrafusal muscle fibers in rat soleus muscles under simulated weightlessness / 生理学报

The present study aimed to study the changes of neurotrophin-3 (NT-3) expression of intrafusal muscle fibers in rat soleus muscles under simulated weightlessness. The tail-suspension (SUS) rat model was used to simulate weightlessness. Forty mature female Sprague-Dawley rats were randomly assigned to ambulatory control (CON), 3-day SUS, 7-day SUS, 14-day SUS and 21-day SUS groups. Immunohistochemistry ABC staining method and enzyme linked immunosorbent assay (ELISA) were used to detect the NT-3 expression of intrafusal muscle fibers in rat soleus muscles. The results from the immunohistochemistry staining technique showed that the extrafusal muscle fibers did not exhibit the NT-3-like immunoreactivity, and NT-3-like immunoreactivity was mainly expressed in nuclear bag 1 and nuclear bag 2 fibers of the muscle spindles. The ELISA results showed that the expression quantity of NT-3 in rat soleus muscles in control, 3-day SUS, 7-day SUS, 14-day SUS and 21-day SUS groups were (14.23±1.65), (14.11±1.53), (13.09±1.47), (12.45±1.51) and (9.85±1.52) pg/mg of tissue respectively. Compared to the control group, the expression quantity of NT-3 was significantly decreased after 14 days of SUS (P<0.05). After 21 days of SUS, the NT-3 expression was further reduced (P<0.01). These results suggest that simulated weightlessness induces an obvious decrease in the NT-3 expression level of intrafusal fibers in rat soleus muscles. Accompanying the simulated weightlessness extension, NT-3 expression in rat soleus muscle spindles is progressively decreased. These changes may contribute to the proprioceptive adaptations to microgravity.

Effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization.</p><p><b>METHODS</b>The immobilization of rat soleus muscle was induced as a disuse muscle model, and 100 Hz sinusoidal vibration was generated by a vibrator and applied to the immobilized soleus muscle, then the changes of H reflex and M wave in muscle were observed after 14 d.</p><p><b>RESULTS</b>Compared to control, after 14 d of immobilization M(max) in soleus muscle decreased (P<0.01), stimulus threshold and S(max) increased (P<0.01); Hmax and H(max)/M(max) decreased (P<0.05, S(max) increased (P<0.05). Compared to immobilized soleus muscle, after 14 d of immobilization with 100 Hz sinusoidal vibration, the M(max) increased(P<0.01), stimulus threshold and S(Mmax) decreased (P<0.05), H(max) (P<0.01) increased and H(max)/M(max) increased (P<0.05).</p><p><b>CONCLUSION</b>100 Hz sinusoidal vibration plays a significant antagonist role against the changes in H reflex and M wave in rat soleus muscle following immobilization.</p>

Association between genetic polymorphisms of ERCC1, XRCC1, GSTP1 and survival of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the association between the polymorphisms of excision repair cross complementation group 1 (ERCC1), X-ray repair cross complementing 1 (XRCC1), glutathione S-transferase Pi 1 (GSTP1) and the survival of advanced gastric cancer patients treated with oxaliplatin-based combination chemotherapy.</p><p><b>METHODS</b>Eighty five patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. Peripheral venous blood was taken before chemotherapy. DNA was extracted from peripheral venous blood. The genetic polymorphisms were detected by real-time PCR assay. The association between time to progression, overall survival and the polymorphisms was analyzed.</p><p><b>RESULTS</b>The median time to progression of the 85 cases was 5.3 months, and the median overall survival was 8.0 months. ERCC1-118 C/C, XRCC1-399 G/G and GSTP1-105 A/G + G/G were favorable genotypes and the number of the favorable genotypes was associated with survival of the patients. The median overall survival was 12.5 months, 10.0 months, 6.5 months and 4.5 months for patients with 3 favorable genotypes, 2 favorable genotypes, 1 favorable genotype and none favorable genotype, respectively, with a significant difference (χ(2) = 35.54, P < 0.01).</p><p><b>CONCLUSION</b>Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with TTP and OS of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based combination chemotherapy as the first-line chemotherapy.</p>

Relationship between prothrombotic state and cardiovescular disease In patients with impaired glucose toler-ance / 中国综合临床

Objective To study the prothrombotic state ,the factors leading to this status,and its relation-ship with the risk of cardiovascular disease in impaired glueese tolerance (IGT) patients. Methods The patients were divided into 4 groups : ①20 control subjects, ②38 patients with IGT, ③20 patients with diabetes only,④31 with diabetes and coronary heart disease. The vWF, throbomodulin, protein C, protein S, plasminogen activator inhibi-tor 1 were measured by ELISA. Results ①)There was statistical difference between IGT and controls in vWF, activi-ty of PC and PAI-1 (P <0.01 ,respectively). ②There were different factors that probably lead to the prothrombotic status among patients with IGT and diabetes. ③There were statistical differences among IGT, diabetes and diabetes with coronary heart disease in vWF, activity of Protein C. There were statistical difference among IGT , diabetes and diabetes with Coronary heart disease in PAI-1 (P < 0.05,respectively). Conclusion ①There is the prothrombotic status in the patients with IGT, similarly to those with diabetes.② IGT has the similar prethrombotic status as diabe-tes, So IGT could be considered as the predromal stage of diabetes, because of some continuity in the progress. Mean-while,it still has some different specialties. ③The abnormality of the system of endothelium, anti-coagulation and fi-brolysis in the patients of IGT is similar to those with diabetes. These variations might have the similar risk of cardio-vascular disease with the diabetes.

Epimedium alleviates chemotherapy-induced damage to the ultrastructure and function of rat epididymides / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the protective action of Epimedium against chemotherapy-induced damage to rat epididymides.</p><p><b>METHODS</b>Fifty 60-day-old male rats were divided into a control, a model and a treatment group. Procarbazine was injected into the abdominal cavity of the model rats at the dose of 30 mg/(kg x d). In addition to procarbazine, Epimedium was given intragastrically to the treatment group. The changes in the ultrastructure of the epididymis were observed after 10 and 20 days.</p><p><b>RESULTS</b>Electron microscopy showed that the chemotherapy-induced damages to the epididymal epithelia mainly included cell swelling, local cavitation of mitochondria, tumor-like change in nucleoli, agglutination of marginal translocation of heterochromatin and cell apoptosis. The damage to the epithelial ultrastructure was slight in the treatment group as compared with the model rats. Chemotherapy significantly affected sperm concentration, sperm viability and sialic acid (SA), which were (15.59 +/- 4.01) x 10(6)/ml, (76.71 +/- 10.11)% and (19.38 +/- 9.34) g/mg prot in the model group in comparison with (10.63 +/- 3.82) x 10(6)/ml (P < 0.01), (60.03 +/- 7.54)% (P < 0.01) and (13.62 +/- 7.81) g/g prot (P < 0.05) in the control. Epimedium significantly increased sperm viability in the treatment group (60.03 +/- 7.54)% as compared with the model rats (69.90 +/- 12.58)% (P < 0.05).</p><p><b>CONCLUSION</b>Epimedium can lessen chemotherapy-induced damage to the epididymis and protect the reproductive function of rats.</p>

Effect of inosine on the discharge of isolated toad muscle spindle / 西安交通大学学报(医学版)

Objective To observe the effect of inosine on afferent discharge of muscle spindle.Methods The afferent discharge of isolated toad muscle spindle was recorded using air-gap technique.The effects of inosine on the discharge rate of muscle spindle was observed.Results After administration of 0.2mmol/L,0.4mmol/L and 0.8mmol/L inosine,the spontaneous discharge of muscle spindle increased from(0.86?(0.12))Hz,(0.88?(0.12))Hz and(0.85?0.10)Hz to(11.42?2.48)Hz,(21.75?3.03)Hz and(32.25?4.08)Hz,respectively.Conclusion Inosine can increase the afferent discharge rate of muscle spindle,and this effect is dose-dependent.

Counteracting effects of high frequency vibration on simulated weightlessness-induced atrophy of soleus muscles in rats / 西安交通大学学报(医学版)

Objective To study counteracting effects of high frequency vibration on simulated weightlessness-induced atrophy of soleus muscles in rats. Methods Female Sprague-Dawley (SD) rats were assigned randomly to one of the three groups: simultaneous control (CON), simulated weightlessness (SUS), and SUS plus high frequency vibration (SUS+HFV). Soleus muscles were examined 7 days later. Sections were treated with adenosinetriphosphatase (ATPase) stain. The cross-sectional areas (CSA) of fibers, the relative proportion of types I and II were measured using Leica image analysis system. Results Compared with those of CON, the wet weight /body of soleus and the cross-sectional areas (CSA) of type I/II fibers in SUS were significantly reduced. The relative proportion of type I fibers in SUS was reduced and type II fibers increased. In SUS+HFV group, the wet weight/body of soleus and the cross-sectional areas (CSA) of type I/II fibers recovered completely. The relative proportion of type I/II fibers recovered completely. Conclusion The present study demonstrates that HFV is effective in counteracting the muscle atrophy induced by simulated weightlessness.

Effects of muscle spindle afferents invoked by intraarterial injection of succinylcholine on the phrenic nerve discharges / 西安交通大学学报(医学版)

ObjectiveTo study wether muscle spindle afferents have the regulating effects on res piratory movement. MethodsExperiments were performed on 36 anesthetized, immobilized, bilater ally vagotomized and artificially ventilated rabbits. Using the phrenic nerve discharge as the respira tory index, this experiment have assessed the effects of muscle spindle afferents invoked by intraarte rial injection of succinylcholine(Sch) on respiration. Results①In 40(63.49% ) cases which had the facilitated effects, 23 (36.51%) cases had the effect of prolonged inspiratory phase and 17 (26.98 % ) cases had the effect of attenuated expiratory phase and augmented respiratory frequency. In addition,there were 11(17.46% ) cases which had the attenuated effects,and 4(6.35% ) cases which had the biphasic effects,and 8(12.7% ) cases which had no effects;②The effect of prolonged inspiratory phase mainly showed the prolongation of inspiratory duration(Ti), but the effect of at tenuated expiratory phase and augmented respiratory frequency mainly showed the decrease of expi ratory duration (Te) and the augmentation of respiratory frequency(RF) ;③The above facilitated ef fects of Sch were significantly attenuated by intramuscular application of bupivacaine to destroy the muscle spindles. ConclusionThese results suggest that muscle spindle afferents induced by intraar terial injection Sch have a significant facilitated effect on respiration.