Ischemic stroke （IS） is an acute cerebrovascular disease caused by insufficient blood supply to the brain， resulting in brain tissue necrosis and neurological dysfunction. It is characterized by impaired motor， language， sensory， cognitive， and other functions. The pathogenesis involves inflammatory responses， excitotoxicity of excitatory amino acids， and mitochondrial dysfunction. IS with a high incidence， high mortality， high disability， and a high recurrence rate is the leading cause of death in China. At present， Western medical therapies mainly focus on vascular recanalization， including thrombolysis and mechanical thrombectomy. However， due to the possibility of cerebral hemorrhage and edema， narrow time windows， and contraindications associated with intravascular therapy， only a few patients can benefit from these therapies， which greatly limit their clinical application. IS belongs to the categories such as stroke， hem iplegia， and major syncope in traditional Chinese medicine （TCM）. It is mainly caused caused by wind， fire， phlegm， and stasis， which lead to imbalance of Yin and Yang， disorder of Qi and blood， and invasion of clear orifices. The common treatment methods include calming the liver and dispelling wind， resolving phlegm and unblocking meridians， and activating blood and resolving stasis. TCM acting on multiple pathways and targets with low toxicity and side effects has definite effects in improving the prognosis and reducing the recurrence rate， being worthy of promotion and research. Brain-derived neurotrophic factor （BDNF） plays a key role in promoting neurogenesis and increasing synaptic plasticity. During the progression of IS， BDNF binds to tyrosine kinase receptor B （TrkB） to initiate intracellular signaling cascades， thus exerting neuroprotective effects. Studies have shown that TCM can regulate the BDNF/TrkB signaling pathway， treating IS by regulating synaptic plasticity and promoting neural repair. This paper summarizes and generalizes the mechanisms of active components， single herbs， and compound prescriptions of TCM in regulating the BDNF/TrkB signaling pathway in the treatment of IS through the review of domestic and foreign literature in recent years， aiming to provide a theoretical basis and treatment reference for the treatment of IS with TCM.

OBJECTIVES: To exple the mechanism of Qixiong Zuogui Granules (QXZG) for enhancing synaptic plasticity in aging rats. METHODS: Forty SD rats were randomized into control group, aging model group, donepezil treatment group, and QXZG treatment group (n=10). Except for the control rats, all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging, and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling. After the interventions, the rats were evaluated for general conditions, behavioral changes, oxidative stress indicators, hippocampal pathologies, and expressions of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, p16, and synaptic plasticity-associated proteins. RESULTS: The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair, body weight loss, and impaired learning and memory abilities, with decreased serum SOD and GSH-Px activities and increased serum MDA level. The rat models also showed obvious pathological changes, reduced Nissl bodies, and elevated p16 protein expression in the hippocampal CA1 region, with significantly decreased expression levels of BDNF, TrkB, CREB and synaptic plasticity proteins SYN, GAP43, and PSD95. Treatment with QXZG alleviated the aging phenotypes in the rat models, improved their learning and memory abilities and pathological changes in the hippocampal CA1 region, reduced oxidative stress and p16 protein expression, and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins. CONCLUSIONS QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins, thereby delaying brain aging and improving learning and memory abilities of the rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Neuronal Plasticity/drug effects* ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism* ; Rats ; Aging ; Drugs, Chinese Herbal/pharmacology* ; Male ; Oxidative Stress ; Hippocampus/metabolism*

Objective To exple the mechanism of Qixiong Zuogui Granules(QXZG)for enhancing synaptic plasticity in aging rats.Method Forty SD rats were randomized into control group,aging model group,donepezil treatment group,and QXZG treatment group(n=10).Except for the control rats,all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging,and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling.After the interventions,the rats were evaluated for general conditions,behavioral changes,oxidative stress indicators,hippocampal pathologies,and expressions of the brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TrkB)pathway,p16,and synaptic plasticity-associated proteins.Results The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair,body weight loss,and impaired learning and memory abilities,with decreased serum SOD and GSH-Px activities and increased serum MDA level.The rat models also showed obvious pathological changes,reduced Nissl bodies,and elevated p16 protein expression in the hippocampal CA1 region,with significantly decreased expression levels of BDNF,TrkB,CREB and synaptic plasticity proteins SYN,GAP43,and PSD95.Treatment with QXZG alleviated the aging phenotypes in the rat models,improved their learning and memory abilities and pathological changes in the hippocampal CA1 region,reduced oxidative stress and p16 protein expression,and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins.Conclusion QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins,thereby delaying brain aging and improving learning and memory abilities of the rats.

Objective·To explore the diagnostic,therapeutic,and prognostic value of metagenomics next-generation sequencing(mNGS)in patients with pneumonia-induced sepsis.Methods·This study consisted of a multicenter,prospective,non-randomized controlled trial and a diagnostic test.Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021.All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine,as well as the clinical diagnostic standard of pneumonia.Enrolled patients were assigned based on their preference to either the conventional test-only group[receiving only conventional test(CMT)]or the combined mNGS test group(receiving CMT and mNGS concurrently).The primary outcome was the 7-day all-cause mortality rate,and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7,28-day all-cause mortality rate,the composite endpoint of mechanical ventilation or death within 28 d,28 d ventilation-free days,28 d hospital-free days,and the average daily hospitalization cost.Propensity score matching was used to balance covariates between the two groups.Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups.Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test.The clinically-adjudicated causative pathogens was used as the reference standard.The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard.The positive percent agreement,negative percent agreement,positive predictive value,and negative predictive value between the two methods and the reference standard were calculated.McNemar's χ2 test was used to evaluate the causative pathogen detection capabilities of the two methods.Results·A total of 533 patients were enrolled,of whom 311 opted for additional mNGS testing,while 222 received only conventional pathogenetic testing.In the non-randomized controlled trial,after propensity score matching to balance covariates,the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group[4.8%vs 8.6%,HR 0.37(95%CI 0.15?0.91),P=0.031].Additionally,the 28-day ventilation-free days were increased in the combined mNGS test group(19.9 d vs 18.4 d,P=0.041).No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs.In the diagnostic test,compared to the reference standard,the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT[91.9%(95%CI 87.7%?95.0%)vs 56.1%(95%CI 49.7%?62.4%),P<0.001].Conversely,the negative percent agreement of mNGS was lower than that of CMT[29.2%(95%CI 18.6%?41.8%)vs 69.2%95%CI 56.6%?80.1%),P<0.001].The negative predictive value of nNGS was higher than that of CMT[48.7%(95%CI 32.4%?65.2%)vs 29.4%(95%CI 22.3%?37.3%),P=0.001].Conclusion·In patients with pneumonia-induced sepsis,mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT.Furthermore,the combination of mNGS with CMT may help reduce the 7-day all-cause mortality,suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

Epicutaneo-cava catheters(ECC)placement plays an important role in fluid management,drug therapy and nutritional support in very low birth weight infants(VLBWI).This study reviews the selection of ECC catheters,preparation for ECC catheterization,catheterization procedures,catheter positioning and tracking,and revelations and recommendations in light of the clinical needs of VLBWI,with the aim of optimizing the clinical management of VLBWI,increasing the success rate of ECC catheterization in NICUs,decreasing the risk of complications,improving the prognosis of the children,and enhancing the quality of their clinical care.

Objective·To explore the diagnostic,therapeutic,and prognostic value of metagenomics next-generation sequencing(mNGS)in patients with pneumonia-induced sepsis.Methods·This study consisted of a multicenter,prospective,non-randomized controlled trial and a diagnostic test.Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021.All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine,as well as the clinical diagnostic standard of pneumonia.Enrolled patients were assigned based on their preference to either the conventional test-only group[receiving only conventional test(CMT)]or the combined mNGS test group(receiving CMT and mNGS concurrently).The primary outcome was the 7-day all-cause mortality rate,and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7,28-day all-cause mortality rate,the composite endpoint of mechanical ventilation or death within 28 d,28 d ventilation-free days,28 d hospital-free days,and the average daily hospitalization cost.Propensity score matching was used to balance covariates between the two groups.Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups.Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test.The clinically-adjudicated causative pathogens was used as the reference standard.The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard.The positive percent agreement,negative percent agreement,positive predictive value,and negative predictive value between the two methods and the reference standard were calculated.McNemar's χ2 test was used to evaluate the causative pathogen detection capabilities of the two methods.Results·A total of 533 patients were enrolled,of whom 311 opted for additional mNGS testing,while 222 received only conventional pathogenetic testing.In the non-randomized controlled trial,after propensity score matching to balance covariates,the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group[4.8%vs 8.6%,HR 0.37(95%CI 0.15?0.91),P=0.031].Additionally,the 28-day ventilation-free days were increased in the combined mNGS test group(19.9 d vs 18.4 d,P=0.041).No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs.In the diagnostic test,compared to the reference standard,the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT[91.9%(95%CI 87.7%?95.0%)vs 56.1%(95%CI 49.7%?62.4%),P<0.001].Conversely,the negative percent agreement of mNGS was lower than that of CMT[29.2%(95%CI 18.6%?41.8%)vs 69.2%95%CI 56.6%?80.1%),P<0.001].The negative predictive value of nNGS was higher than that of CMT[48.7%(95%CI 32.4%?65.2%)vs 29.4%(95%CI 22.3%?37.3%),P=0.001].Conclusion·In patients with pneumonia-induced sepsis,mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT.Furthermore,the combination of mNGS with CMT may help reduce the 7-day all-cause mortality,suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

Epicutaneo-cava catheters(ECC)placement plays an important role in fluid management,drug therapy and nutritional support in very low birth weight infants(VLBWI).This study reviews the selection of ECC catheters,preparation for ECC catheterization,catheterization procedures,catheter positioning and tracking,and revelations and recommendations in light of the clinical needs of VLBWI,with the aim of optimizing the clinical management of VLBWI,increasing the success rate of ECC catheterization in NICUs,decreasing the risk of complications,improving the prognosis of the children,and enhancing the quality of their clinical care.

ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL^-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d^-1）， and low- and high-dose （crude drug 3.4， 17 g·kg^-1·d^-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL^-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg^-1） group， and low- and high-dose （8.4 and 33.6 g·kg^-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

Parkinson's disease （PD） is a common neurological degenerative disease in the middle-aged and elderly， characterized by pathological changes of progressive degeneration of dopaminergic neurons in the substantia nigra and Lewy body formation， with high prevalence and long course of disease. The drug is mainly used to treat PD in western medicine， and the early curative effect is remarkable. However， with the progression of the disease and the long-term use of the drug， the efficacy will be significantly reduced， or there may be sports complications， and the long-term efficacy is not good. As a traditional medical system， traditional Chinese medicine has a unique understanding of PD. Traditional Chinese medicine plays an important role in the treatment of PD， which is natural， mild， safe， and effective， and it can cooperate with western medicine to enhance its efficacy and reduce the adverse reactions of western medicine. The pathogenesis of PD is complex， involving multiple levels such as mitochondrial dysfunction and apoptosis. Neuroinflammation is also involved in the progressive degeneration of dopaminergic neurons in PD. The Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway is a classic inflammatory pathway， and its expression changes play an important role in the occurrence and development of inflammatory response in the body. In recent years， the research on this pathway in TCM is increasing. This paper summarized the literature of traditional Chinese and western medicine in the past 10 years and reviewed the relevant mechanism of TCM regulation of TLR4/NF-κB pathway in the treatment of PD from the aspects of TCM monomer， compound， and other TCM therapies， so as to provide some references for the search for new targets of drug therapy and gene therapy and the in-depth study of TCM prevention and treatment of PD.