Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study.

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV1/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF25%-75%, t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

Qian-Zheng-San promotes regeneration after sciatic nerve crush injury in rats.

Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San (1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that Qian-Zheng-San has a positive effect on peripheral nerve regeneration.

Local administration of icariin contributes to peripheral nerve regeneration and functional recovery.

Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration.

Efficacy and safety of rivaroxaban versus low-molecular-weight heparin therapy in patients with lower limb fractures.

Thromboprophylaxis with rivaroxaban has proved effective and safe in patients undergoing hip and knee replacement surgery. As it is unclear whether it is also effective and safe in fracture patients, the aim of the present study was to evaluate the efficacy and safety of rivaroxaban in patients with lower limb fractures. We performed a retrospective cohort study of 2,050 consecutive patients treated for lower limb fractures at our trauma center, comparing rates of venous thromboembolism (VTE), bleeding and surgical complications, and the length of hospital stay for 608 patients who received rivaroxaban and 717 who received a low-molecular-weight heparin (LMWH). Rates of symptomatic VTE were 4.9 and 8.6% in the rivaroxaban and LMWH groups, respectively (p = 0.008), and distal VTE rates were 1.8 and 5.7%, respectively (p = 0.036). The incidence of major bleeding events in the rivaroxaban group was also lower than in the LMWH group (0.2 vs 0.6%), but the difference between the groups was not statistically significant. The mean length of hospital stay was significantly shorter in the rivaroxaban group (12.2 vs 13.1 days, respectively; p = 0.016). This retrospective cohort study is the first report documenting the efficacy and safety of rivaroxaban in patients with lower extremity fractures. In comparison with LMWH, rivaroxaban reduced the incidence of VTE by 45% without increasing the risk of bleeding. However, prospective, randomized controlled trials comparing rivaroxaban and LMWH are needed to confirm our findings.

[Radix hedysari extract promotes peripheral nerve regeneration].

Treatment of peripheral nerve injury is a major challenge in clinical practice. With advances in molecular biology and development of microsurgical techniques and tissue engineering, peripheral nerve repair procedures have been greatly improved. In the last 10 decades, most treatments for peripheral nerve injury in animal models have achieved histological and functional recovery, the treatments in humans, however, produce insufficient recovery, especially for proximal nerve injury. Increasing attention has been paid to the Traditional Chinese Medicine (TCM) for promoting peripheral nerve regeneration, since these remedies often display effective clinical outcome, minor side effects and effectiveness for multiple targets. Although TCM has complex ingredients and the specific pharmacological mechanisms for their effectiveness are still unclear, an effective clinical outcome is welcomed by many clinicians. In the past 20 years, we have made a series of detailed studies including the toxicity tests, pharmacodynamic tests, pharmacological experiments etc, about a new traditional formula which mainly contains the Radix hedysari, Epimedium etc. RESULTS have shown that this formula is safe to be used in both animals and humans with no toxicity and adverse effect, and systemic administration of this formula could enhance the peripheral nerve regeneration.

Epimedium extract promotes peripheral nerve regeneration in rats.

Effects of Epimedium extract and its constituent icariin on peripheral nerve repair were investigated in a crush injury rat model. Animals were divided into four groups: sham, control, Epimedium extract, and icariin groups. At postoperative weeks 1, 2, 4, and 8, nerve regeneration and functional recovery were evaluated by sciatic functional index (SFI), nerve electrophysiology, nerve pinch test, and muscle wet weight. Results showed that at 2 and 4 weeks after surgery rats in the Epimedium group displayed a better recovery of nerve function than that in the icariin and control groups, with better recovery in the icariin group than in the control group. The nerve pinch test showed that nerve regeneration was greater in the Epimedium group and the icariin group as compared to the control group. In addition, the muscle wet weight in the Epimedium group was significantly improved when compared with the icariin group, and the improvement in the icariin group was better than that in the control group at 8 weeks after operation. Our findings suggest that Epimedium extract effectively promotes peripheral nerve regeneration and improves the function of damaged nerves.

Hedysari extract improves regeneration after peripheral nerve injury by enhancing the amplification effect.

Radix Hedysari is an herbal preparation frequently used in traditional Chinese medicine. It can promote regeneration after peripheral nerve injury, but its effect on the amplification ratio (the ratio of distal to proximal fibers) during peripheral nerve regeneration has not yet been examined. In this study, we explored the effect of Hedysari extract on the amplification ratio in the peripheral nerve. Male Sprague-Dawley rats were separated into three groups at random: normal group (without surgery), model group (given sleeve nerve bridging surgery, but without adjuvant treatment) and treatment group (given sleeve nerve bridging surgery and then given Hedysari extract as adjuvant treatment). Twelve weeks after surgery, general observations, electrophysiological examination, histological analysis, morphometric measurements, and amplification ratio calculations were made. The results showed that nerve conduction velocity, the fiber and axon diameter, the g-ratio, the number of regenerating nerve fibers and the amplification ratio were better in the treatment group than in the model group, suggesting that Hedysari extract can effectively promote the growth of lateral buds in the proximal nerve stump and substantially improve the amplification effect during peripheral nerve regeneration.

Lumbricus extract promotes the regeneration of injured peripheral nerve in rats.

BACKGROUND: Earthworms regenerate amputated parts of their body if the nervous system is intact. Lumbricus is one traditional Chinese medicine (TCM), which has been used in China to promote nerve function for hundreds of years. AIM OF THE STUDY: To investigate the beneficial effect of lumbricus extract on peripheral nerve regeneration in rats. MATERIALS AND METHODS: Nerve function was surgically impaired in Sprague-Dawley (SD) rats by clamping of the left sciatic nerve. The sham-operated group (surgery but no sciatic nerve clamping), control group, and treatment group were treated with 2 ml 0.9% NaCl, 0.9% NaCl, and lumbricus extract (1g/ml), respectively. Treatments were administered once daily after the operation for 6 weeks. During this period, motor function was monitored by walking track analysis, conduction function of injured sciatic nerve was monitored by electrophysiology, and regeneration of myelinated nerve was assessed by immunohistochemistry. RESULTS: (1) For nerve function index value, treatment group is higher than control group. (2) For conduction velocity of injured sciatic nerve, treatment group is higher than control group at week 3 and 6. (3) For the number of regenerated myelinated nerve fibers, treatment group is higher than control group at week 2 and 6. CONCLUSIONS: Lumbricus extract appears to enhance sciatic nerve regeneration and function recovery following injury, suggesting the clinical potential of lumbricus extract on the treatment of peripheral nerve injury in humans.

Effects of Hedysari polysaccharides on regeneration and function recovery following peripheral nerve injury in rats.

It has been demonstrated that aqueous extract of Radix Hedysari Prescription and modified Radix Hedysari Prescription could improve the regeneration of injured peripheral nerve. Radix Hedysari is a main component in these two formulas. We hypothesized that Hedysari polysaccharides (HPS), a main active ingredient, could also enhance peripheral nerve regeneration after nerve injury in adult animals. In the present study, we examined the effects of HPS on sciatic nerve regeneration for 6 weeks following clamping in rats (administrated orally of 2 ml HPS liquid daily, 0.25 g/ml). The results showed that HPS was able to enhance sciatic function index (SFI) value, tibial function index (TFI) value, peroneal nerve function index (PFI) value, conduction velocity, and the number of regenerated myelinated nerve fibers, suggesting the potential clinical application of HPS for the treatment of peripheral nerve injury in humans.

[Traditional Chinese medicine and formulas of improving peripheral nerve regeneration].

Peripheral nerve impairment is a common complication in surgery, which repair relates directly to the recovery of motor function and sensory function. Clinical researchers always do nerve sutrure using microsurgical technique and adjuvant treatment to improve peripheral nerve regeneration. Western medicine used usually of adjuvant drugs, such as neurotrophic factors, are limited by their defects in clinical application. Traditional Chinese medicine classifies peripheral nerve impair as paralysis and arthromyodynia, considers that it is the result of defects of meridian and vessels, QI and blood, bones and muscles. So, drugs used usually are QI invigorating herbs, blood circulation promoting herbs for unblocking collaterals, and nourishing herbs, including astragali, hedysari, ginkgo leaf, angelica, danshen root, paeoniae radix, epimedium, chuanxiong, and common basic formulas, such as Buyang Huanwu decoction, Huangqi Guizhi Wuwu decoction, Huoxue Kangyuan decoction, compound radix hedysari, etc. To be ready for further study and development, we review the traditional Chinese medicine and formulas in this article.

[Primary study on effect of various components of modified formula radix hedysari on peripheral nerve regeneration].

OBJECTIVE: To investigate the effects of icariin and mixed prescription of icariin, radix hedysari polysaccharide, and liquid extracted from earthworm on peripheral nerve regeneration. METHODS: Twenty male SD rats weighing (200 +/- 10) g were selected and randomized into four groups (n=5 per group): sham operated group (group A), model group (group B), icariin group (group C), and mixed liquid group (group D). In group A, the left sciatic nerves of the rats were only exposed, and treated at fixed time from the following day with the NS (2 mL/d). In groups B, C, D, the models were made by clamping sciatic nerve and treated with NS, icariin and mixed liquid, respectively (2 mL/d). The general state of animals was observed after the treatment daily. The nerve function index, motor nerve conductive velocity and the amorphous and number of myelinated sciatic nerve fibers were measured at 21 days. RESULTS: Animals in various groups were all in good state. After 21 days, the weights of rats in groups A, B, C and D were (366.9 +/- 14.0), (370.1 +/- 16.3), (373.3 +/- 19.6) and (374.0 +/- 11.4) g, respectively, and there was no significant difference among these groups (P > 0.05). For sciatic function index, there was no significant difference between group A and group D (P > 0.05), between group B and group C (P > 0.05), while there was significant difference between group B and group D (P < 0.05). For tibial function index, there was significant difference between group A and groups B, C, D (P < 0.05), there was no significant difference between group B and groups C, D (P > 0.05). For peroneal function index, there was no significant difference between group A and groups C, D (P > 0.05), between group B and groups C, D (P > 0.05). The sciatic motor nerve conductive velocities of group A, B, C and D were (45.0 +/- 2.9), (8.0 +/- 2.6), (13.4 +/- 6.8), and (19.6 +/- 9.3) m/s, respectively, there was no significant difference between group B and group C (P > 0.05), and there was significant difference between group A and groups B, C, D and between group B and group D (P < 0.05). The size of individual myelinated sciatic nerve fibers of regenerated nerves in groups B, C, and D was significantly smaller than that in group A. Comparing with group A, the number of myelinated sciatic nerve fibers in groups B, C, and D was 93.3% +/- 35.6%, 90.6% +/- 37.1%, and 115.4% +/- 40.6%, respectively, but there was no significant difference among four groups (P > 0.05). CONCLUSION: Icariin and mixed prescription are safe. The improving peripheral nerve regeneration effect of mixed prescription is more obvious than that of icariin, indicating the comprehensive study of modified formula radix hedysari is necessary to find the effective part or mixture of effective compounds with fixed percentage.

Compound injection of radix Hedysari to promote peripheral nerve regeneration in rats.

OBJECTIVE: To study the effect of compound injection of Radix Hedysari on peripheral nerve regeneration in rats. METHODS: Seventy-five healthy adult SD male rats, weighing 150 g, were randomized into 5 groups (15 rats in each group). The bilateral sciatic nerves of the rats were exposed and clamped with a smooth clamp to make an injury area of 2 mm. After clamp operation Group 1 was injected with compound injection of radix Hedysari (CIRH) 1.5 ml/day, Group 2 with CIRH 1.0 ml/day, Group 3 with CIRH 0.5 ml/day, Group 4 with nerve growth factor (NGF) 50 U/day, and Group 5 was taken as the control group without any management. The bilateral sciatic nerve was taken out at 3 days, 1, 2 and 4 weeks after clamping, stained with osmic acid and observed microscopically. The myelinated nerve fibers were counted. The nerve conduction velocity was determined 2 and and 4 weeks before sample taking the sciatic nerve function index was measured 4 weeks before sample taking. RESULTS: The results of nerve conduction velocity, the myelinated nerve fiber count and the sciatic functuion index in the CIRH treated groups were better than those in the control group. The results of the nerve conduction velocity and the myelinated nerve fiber count at 2 weeks and the nerve conduction velocity at 4 weeks in Group 1 were better than those of Group 4. Biological observation showed that degenerated and necrotic myelin sheath in CIRH treated Groups at 2 and 4 weeks decreased remarkably compared to the NGF treated group. CONCLUSIONS: CIRH can promote regeneration of peripheral nerves and absorption of degenerated and necrotic injured nerves. It has the same effect as NGF.