BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring,and the advantages of Chinese medicine such as many targets,wide range,rich mechanisms,and few side effects have great potential in the treatment of various diseases. OBJECTIVE:Based on the nuclear transcription factor kappa B signaling pathway,this paper systematically expounded and summarized the research progress of kaempferol,safflower yellow,baicalin,and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS:Search terms"spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids"were searched in CNKI and PubMed databases.Totally 67 articles were finally included. RESULTS AND CONCLUSION:(1)The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse,which can regulate neutrophils,microglia,astrocytes,and macrophages,and mediate the occurrence and development of inflammation after injury.(2)The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein,the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway,and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body,thereby promoting the recovery of neurological function.(3)The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury,and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury.Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors,improve the antioxidant capacity of cells,and promote the activation of immune cells,but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis.(4)Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway,how to achieve precise intervention for nervous system inflammation and injury,and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways,in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases.

ObjectiveTo investigate the effects of modified Chunzetang on urinary retention in rats with spinal cord injury （SCI） and the c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathway. MethodBefore modeling， 10 of the 70 female SD rats were randomly selected to assign to the blank group， and 10 to the sham group. The remaining 50 rats were used to prepare a SCI-induced urinary retention model using the spinal cord transection method. The model rats were randomly divided into model group， low-dose modified Chunzetang group， high-dose modified Chunzetang group， and inhibitor group. After modeling， the blank group， sham group， and inhibitor group were given 2 mL of saline by gavage. The high-dose and low-dose groups of modified Chunzetang were given modified Chunzetang at 28.8 g·kg^-1 and 14.4 g·kg^-1 by gavage， respectively. The inhibitor group was injected intraperitoneally with the JNK inhibitor SP600125 twice a week at a dose of 15 mg·kg^-1. All rats were gavaged for a total of 28 days. Urodynamic and bladder muscle tension tests were conducted to evaluate bladder function. Hematoxylin-eosin （HE） staining was performed to observe the morphology of bladder smooth muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of JNK， phosphorylated （p）-p38 MAPK， B cell lymphoma-2 （Bcl-2）， and cysteinyl aspartate-specific proteinase-3 （Caspase-3）. Western blot was used to detect the expression levels of p-JNK， p-p38 MAPK， ETS-like protein-1 （ELK-1）， and activator protein-1 （AP1） in the detrusor muscle. Immunofluorescence was used to detect the expression levels of p-JNK， p-p38 MAPK， and AP1. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay was conducted to measure cell apoptosis. ResultCompared with blank group and sham group， the model group showed a significant increase in maximum bladder capacity and bladder compliance， and a significant decrease in leak point pressure. The minimum contraction force was increased， and the contraction frequency was significantly decreased （P<0.01）. The structure of bladder smooth muscle was disordered， with a large number of vacuolar cells， tissue edema， mononuclear cell infiltration， obvious hemorrhage， and a trend towards fibrosis in connective tissue. TUNEL positive cells increased significantly. The protein expression levels of p-JNK， p-p38 MAPK， AP1， and ELK-1 were significantly increased （P<0.01）. Compared with model group， all intervention groups showed significant improvement in urodynamic and bladder muscle contraction tests. In the low-dose modified Chunzetang group， the levels of p-p38 MAPK and Caspase-3 was decreased （P<0.05，P<0.01）. The levels of JNK, p-p38 MAPK and Caspase-3 in the high-dose group were significantly decreased （P<0.01）， and the level of Bcl-2 was significantly increased （P<0.01）. The expression levels of p-JNK， p-p38 MAPK， and AP1 proteins were significantly reduced （P<0.01）， and ELK-1 protein expression was decreased （P<0.05）. The positive rate of p-JNK and AP1 receptors was significantly decreased （P<0.01）. The positive cell rate was significantly decreased （P<0.01）. The high-dose modified Chunzetang group was positioned between the low-dose group and the inhibitor group， with no significant difference compared to the inhibitor group. ConclusionModified Chunzetang can improve urinary retention in SCI and enhance the contraction force of bladder smooth muscle. This effect is related to the inhibition of the JNK/p38 MAPK signaling pathway activation， thereby reducing apoptosis of bladder smooth muscle cells.

Objective We investigated the effects of Xueguan Ruanhua Pills(XGRHW) on ferroptosis in ApoE-/- atherosclerotic mice through the nuclear factor E2 related factor 2 (Nrf2)/xCT/glutathione peroxidase 4 (GPX4) signaling pathway.Methods Ten male C57BL/6J mice in the normal group were fed normal chow. Additionally, 50 ApoE-/- mice were fed high-fat chow for 12 weeks, and were divided into the following five groups (10 mice per group): the model group, the XGRHW low-dose (2.34g/kg) group, the XGRHW high-dose (4.68 g/kg) group, the XGRHW high-dose combined with the Nrf2 inhibitor ML385 (0.03 g/kg) group, and the ferrostatin-1 (1 mg/kg) group. Drugs were administered for 6 weeks. The blood levels of four types of lipids were detected by an automatic lipid analyzer, lipid deposition in the aorta was observed by Oil Red O staining, histomorphological changes in the aortic sinus were observed by HE staining, the serum levels of Fe2+, MDA, GSH, and SOD were determined by colorimetric assays, and the expression levels of FTH1 and FTL in the aortic sinus were observed by immunofluorescence. The protein levels of Nrf2, xCT, and GPX4 in mouse aortic tissues were detected by Western blotting. The ultrastructural changes of aortic mitochondria were observed by transmission electron microscopy.Results Compared with the normal group, mice in the model group showed obvious lipid plaque deposition in the aorta, severely calcified lesions in the aortic sinus, elevated serum levels of TC, TG, LDL-C, Fe2+, and MDA, decreased levels of HDL-C, SOD, and GSH (P<0.01), and decreased protein expressions of aortic Nrf2, xCT, and GPX4 as well as the iron storage proteins FTH1 and FTL (P<0.01), and serve damage to mitochondrial structure and morphology. Compared with the model group, the relative aortic plaque area was decreased, calcified lesions in the aortic sinus were decreased, serum levels of TC, TG, LDL-C, Fe2+, and MDA were decreased, and HDL-C, SOD, and GSH levels were increased in the XGRHW low-dose and high-dose and ferrostatin-1 groups (P<0.05 or P<0.01), and Nrf2, xCT, GPX4, and the iron storage proteins FTH1 and FTL were upregulated in aortic tissues (P<0.05 or P<0.01), and mitochondrial structure approaching normal. In the XGRHW high-dose+ML385 group, compared with the XGRHW high-dose group, the levels of blood lipids and lipid peroxidation were increased and the protein levels of Nrf2, xCT, and GPX4 in aortic tissue and the iron storage proteins FTH1 and FTL were decreased (P<0.01), and mitochondrial structure was damaged indicating that ML385 could inhibit the therapeutic effect of the XGRHW in atherosclerotic mice.Conclusion The XGRHW can improve blood lipid levels and reduce the degree of arterial plaque lesions in atherosclerotic mice, and its mechanism of action may be related to activation of the Nrf2/xCT/GPX4 pathway to inhibit ferroptosis.

Objective To observe the therapeutic effect of extracorporeal shock wave therapy combined withsurface electromyography biofeedback training(ESW-sEMGBF)on post-traumatic elbow joint stiffness.Methods A total of 80 patients with post-traumatic elbow stiffness admitted to the Rehabilitation Department of Hangzhou Fuyang Hospital of Orthopedics of Traditional Chinese Medicine from January 2021 to December 2021 were randomly assigned into control group(n = 40)and treatment group(n = 40)using a lottery method.The control group received conventional rehabilitation treatment(including soft tissue release,joint mobilization,continuous passive motion and cold therapy),and the treatment group received conventional treatment combined with ESW-sEMGBF.Both groups underwent training once daily for five days a week over eight weeks.The visual analogue scale(VAS),active range of motion(AROM)of the elbow joint,and Mayo Elbow Performance Score(MEPS)were evaluated before and after treatment.Results After 8 weeks of treatment,significant improvements were observed in all outcomes for both groups.The treatment group showed better improvements in VAS scores,AROM,and MEPS after treatment compared with the control group(P<0.05,P<0.001,P<0.001).No side effects or adverse reactions were observed in either group after treatment.Conclusion Extracorporeal shock wave therapy combined with surface electromyography biofeedback training effectively alleviated pain in patients with post-traumatic elbow joint stiffness,improved elbow joint function,and increased active range of motion of the elbow joint.

Objective To observe the clinical efficacy of closed-loop rehabilitation therapy by brain-computer interface(BCI)combined with exoskeleton robotic hand in patients with hand dysfunction after cerebral infarction and analyze the influence of patients'cognitive function and implicit motor imagery ability on the recognition rate of BCI.Methods A total of 50 patients with cerebral infarction were randomly assigned to the observation group and the control group,25 patients in each group.Both groups received routine rehabilitation programs.In addition to the conventional rehabilitation treatment,the observation group received the closed-loop BCI rehabilitation trainingby brain-computer interface(BCI)combined with exoskeleton robotic hand.The scores of Fugl-Meyer Assessment of the Upper Extremity(FMA-UE),Action Research Arm Test(ARAT),Wolf Motor Function Test(WMFT),and Modified Ashworth scale(MAS)of the wrist flexors were compared between the two groups before and after treatment.Before intervention,the mental rotation test and Montreal Cognitive Assessment(MoCA)were used to assess the baseline implicit motor imagery ability and cognitive level of patients in the observation group.The correlation analysis between these scores and the recognition rate of BCI was conducted to analyze the relevant factors affecting the closed-loop rehabilitation effects of BCI.Results The two groups showed no significant difference in all outcomes before treatment(both P>0.05).After intervention,the observation group exhibited the significantly higher scores of FMA-UE,ARAT,and WMFT(all P<0.05),and significantly lower MAS scores of wrist and finger flexors compared with the control group(all P<0.05).In addition,the recognition rate of BCI was positively correlated with the accuracy of mental rotation test and MoCA score(P<0.05),and negatively corre-lated with the reaction time of mental rotation test(P<0.05).Conclusions Closed-loop rehabilitation training with BCI combined with exoskeleton robot hand can promote the recovery of upper limbs and hand motor function in patients with cerebral infarction.Additionally,the implicit motor imagery ability and cognitive function of patients are suggested to be used for screening the patients suitable for BCI training before the implementation of BCI treatment.

【Objective】 To analyze the preliminary screening and follow-up testing data of HBV in Yantai area, and discuss the rationality of following up and re-entry program of HBV reactive blood donors. 【Methods】 Donors who were single reagent reactive by enzyme-linked immunosorbent assay (ELISA) in initial screening but non-reactive by nucleic acid testing (NAT) were followed up. Individual NAT(ID-NAT) was performed for HBV DNA, ELISA for HBsAg, HBsAb, HBeAb, HBeAg and HBcAb, and ECLIA for the detection of HBsAg. 【Results】 A total of 547 blood donors were HBsAg ELISA-/NAT+, and 97 were followed up, among which 24 met the requirements of re-entry while 73 did not. Of the 24 blood donors who met the re-entry requirements, 13 donated blood again, with test results all qualified. 【Conclusion】 The combination of ELISA, ID-NAT, and ECLIA methods for following up detection for HBsAg ELISA+ blood donors is recommended. Blood donors with HbsAb S/CO ≥ 10 and negative results for other tests met the re-entry requirements, with a re-entry rate at 24.74%, and the re-donation qualified rate of blood donors after re-entry was 100%.

The injury of vascular endothelial cells is not only the initial condition to promote the occurrence of early atherosclerosis （AS） plaques， but also an important link in the pathogenesis of AS. The microRNA （miRNA）， as an important medium of intercellular communication and gene regulatory factor， can affect vascular endothelial function and participate in the development of AS. The molecular mechanism of miRNA’s multi-target intervention in vascular endothelial cell injury has become a hot topic in the research of cardiovascular diseases. Monomers of traditional Chinese medicines such as ginsenoside Rb2 and paeonol， as well as traditional Chinese medicine for resolving phlegm and removing blood stasis could regulate miRNA to improve endothelial cell inflammation； astragaloside Ⅳ， dihydromyricetin and notoginsenoside could target miRNA and inhibit vascular endothelial oxidative stress； Danhong injection， Jianpi qutan and huayu prescription and paeonol could affect endothelial autophagy through miRNA； resveratrol， Bushen huoxue formula and Bushen tongmai formula could inhibit vascular endothelial aging by miRNA； dendrobine played an active role in regulating miRNA and improving endoplasmic reticulum stress. In the future， more in- depth research is needed on the effectiveness， mechanism of action， diagnosis and treatment plans， and safety of targeted regulation of miRNA for AS therapy by traditional Chinese medicine.

Stroke is a disease with a high disability rate， and often leads to limb dysfunction， especially upper limb motor dysfunction， which significantly affects the patients’ abilities and quality of life. With patients' increasing demand for functional recovery， various therapeutic techniques of rehabilitation medicine have been rapidly developed. As an important active central intervention technology， motor imagery training can be initiated by the patient's brain and activate the sensorimotor network to accelerate the repair of limb functions. The development of preventive medicine has promoted the continuous evolution of the concept of rehabilitation. The strategies of full cycle functional protection and disability prevention have been improved and developed in the clinical and scientific research practice of upper limb rehabilitation after stroke. The motor imagery training can activate the upper limb motor neural network in the early stage of stroke to prevent functional loss； In the recovery period， it can accelerate the neural function remodeling and reduce the upper limb disability； In the later stage after stroke， it can improve the performance of upper limb function in daily life， thus helping patients return to family life and society. This article reviews the research progress in recent years in China and abroad in the application of motor imagery training for the full cycle function protection and disability prevention of stroke.

Objective:To explore the mechanism of motor imagery training (MIT) combined with conventional rehabilitation to promote the functional recovery of upper limbs in stroke survivors. To explore the brain network reorganization resulting when motor imagery training (MIT) is combined with conventional rehabilitation to promote the motor recovery of stroke survivors.Methods:Fourteen hemiplegic patients were recruited as the MIT group. They underwent 4 weeks of MIT (30 min/day, 5 days/week) along with conventional rehabilitation treatment. The upper limb section of the Fugl-Meyer assessment (FMA-UE) and the modified Barthel Index (MBI) were used to assess all of the patients, and resting-state fMRI was performed before and after the treatment. Twenty-eight age- and sex-matched healthy subjects also received one-time resting-state fMRI scanning. Granger causal analysis was performed in the MIT group to calculate the changes in effective connection between the ipsilesional primary motor cortex and the whole brain before and after the treatment, and the results were compared with the healthy control group.Results:After the treatment, the average FMA-UE and MBI of the MIT group had increased significantly. Before the intervention, the effective connection mode of the ipsilesional M1 area in the MIT group was significantly different from that of the healthy controls. The causal flow from the ipsilesional M1 area to the bilateral prefrontal cortex had increased abnormally and the causal flow from the contralesional primary motor cortex, the inferior parietal lobule and the cerebellum to the ipsilesional M1 area had decreased significantly. After the treatment, the effective connection pattern of the stroke survivors was nearly normal, and the causal influence from contralesional motor imagery-related brain areas (the superior parietal lobule, inferior parietal lobule, thalamus and the fusiform gyrus) to the ipsilesional M1 area was enhanced. Effective connection from the ipsilesional M1 area to the contralesional cerebellum before the intervention was positively correlated with the improvement in FMA-UE scores, and the effective connection from the contralesional middle frontal gyrus to the ipsilesional M1 area was correlated negatively.Conclusions:The neural mechanism of MIT's effectiveness when it is combined with conventional rehabilitation might be related to the reorganization of effective connections. That would include enhanced causal flow between motor imagery-related brain areas and the contralesional cerebellum and ipsilesional M1 area. Down-regulation of the effective connection from the contralesional middle frontal gyrus to the ipsilesional M1 area also occurs.