Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Notoginsenoside R_1 interferes with renal oxidative stress and Nrf2/HO-1 signaling pathway to alleviate kidney injury in mice with IgA nephropathy and its mechanism / 中国中药杂志

The purpose of this study was to investigate the effect of notoginsenoside R_1(NGR_1) on alleviating kidney injury by regulating renal oxidative stress and the Nrf2/HO-1 signaling pathway in mice with IgA nephropathy(IgAN) and its mechanism. The mouse model of IgAN was established using a variety of techniques, including continuous bovine serum albumin(BSA) gavage, subcutaneous injections of carbon tetrachloride(CCl_4) castor oil, and tail vein injections of lipopolysaccharide(LPS). After successful modeling, mice with IgAN were randomly separated into a model group, low, medium, and high-dose NGR_1 groups, and a losartan group, and C57BL6 mice were utilized as normal controls. The model and normal groups were given phosphate buffered saline(PBS) by gavage, the NGR_1 groups were given varying dosages of NGR_1 by gavage, and the losartan group was given losartan by gavage for 4 weeks. The 24-hour urine of mice was collected after the last administration, and serum and kidney tissues of mice were taken at the end of the animal experiment. Then urine red blood cell count(URBCC), 24-hour urine protein(24 h protein), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were measured. The enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of galactose-deficient IgA1(Gd-IgA1), kidney injury molecule 1(Kim-1), and neutropil gelatinase-associated lipocalin(NGAL) in the mouse serum. The assay kits were used to detect the levels of malondialdehyde(MDA) and superoxide dismutase(SOD), and immunofluorescence(IF) was used to detect the expression level of glutathione peroxidase 4(GPX4) in the mesangial region. Western blot was used to detect the protein expression of nuclear transcription factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway in the renal tissue. Hematoxylin-eosin(HE) staining was used to observe pathological alterations in the glomerulus of mice. The results revealed that, as compared with the model group, the serum Gd-IgA1 level, URBCC, 24 h protein level, renal damage markers(Kim-1 and NGAL) in the high-dose NGR_1 group decreased obviously and renal function indicators(BUN, Scr) improved significantly. The activity of SOD activity and expression level of GPX4 increased significantly in the high-dose NGR_1 group, whereas the expression level of MDA reduced and protein expression levels of Nrf2 and HO-1 increased. Simultaneously, HE staining of the renal tissue indicated that glomerular damage was greatly decreased in the high-dose NGR_1 group. In conclusion, this study has clarified that NGR_1 may alleviate the kidney injury of mice with IgAN by activating the Nrf2/HO-1 signaling pathway, improving antioxidant capacity, and reducing the level of renal oxidative stress.

Clinical characteristics and drug efficacy evaluation of voltage-gated potassium channel-related genetic epilepsy / 中国药理学通报

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

Determination of cobalt and tungsten in human urine by inductively coupled plasma mass spectrometry / 中华劳动卫生职业病杂志

Objective: To establish a inductively coupled plasma mass spectrometry method for the determination of trace cobalt and tungsten in human urine. Methods: The authors used 1% nitric acid solution as diluent in October-December 2021, the sample dilution factor and internal standard element were optimized by single factor rotation experiment, and the difference between the working curve and the standard curve was compared. Results: The method uses working curve to determine cobalt and tungsten in urine, the linear range of this method was 0.0~10.0 μg/L, the correlation coefficient was 0.999 9, the detection limits respectively were 0.005 μg/L (cobalt) and 0.09 μg/L (tungsten), the recoveries of samples respectively were 87.0%~100.2% (cobalt) and 89.4%~104.8% (tungsten), the relative standard deviations respectively were 0.4%~4.4% (cobalt) and 0.6%~3.8% (tungsten) . Conclusion: A simple and rapid method for determination of cobalt and tungsten in urine has been established. This method has the advantages of simple operation, high sensitivity, low detection limit and good stability. It is suitable for determination of cobalt and tungsten in urine of all kinds of people.

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/β-catenin signaling / 亚洲男科学杂志(英文版)

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ β-catenin signaling. Western blot revealed that the expression of β-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Survival analysis of unexpected small cell lung cancer following surgery / 中华肿瘤杂志

Objective: To investigate the survival and influencing factors of unexpected small cell lung cancer following surgery. Methods: We respectively reviewed the clinical characters of 104 patients who underwent surgical treatment and be proved as small cell lung cancer by pathology between January 2000 to October 2020 in Chinese PLA General Hospital. Overall survival (OS) of patients was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Results: Of 104 patients, 27 cases showed central lesions, and other 77 showed peripheral nodules. The margin of nodules was smooth in 42 cases on CT imaging. The median OS was 34.3 months and 5-year OS rate was 45.8%. Postoperative 5-year OS rates for patients were 52.1%, 45.4%, and 27.8% for clinical stages Ⅰ, Ⅱ, and Ⅲ, respectively. Univariate analyses identified the age, surgical access, surgical approach, N stage, TNM stage and vascular cancer emboli were associated with OS (P<0.05). The N stage was an independent factor for the OS of patients (P<0.05). Conclusions: Patients with unexpected SCLC, including Ⅰ, Ⅱ and part ⅢA stage have favorable outcome and can benefit from surgery and systemic postoperative treatment. Standard lobectomy plus systemic lymph node dissection is commended.

Intraoperative assisted O-arm navigation imaging for unstable pelvic fractures in INFIX / 中国骨伤

OBJECTIVE@#To investigate the effect of internal external fixator assisted O-arm navigation imaging in the treatment of unstable pelvic fractures.@*METHODS@#From May 2019 to November 2019, 15 patients with unstable pelvic fractures were treated by intraoperative O-arm navigation imaging using INFIX technology. There were 6 males and 9 females. The age ranged from 24 to 66 years old. The course of disease ranged from 2 to 14 days. According to Tile classification, there were 1 case of B1 type, 8 cases of B2 type, 3 cases of C1 type, and 3 cases of C2 type. According to Young-Burgess classification, there were 8 cases of LC, 1 case of APC, 4 cases of VS, 2 cases of CM. Preoperative routine pelvic anteroposterior film, entrance position, exit position and pelvic CT three-dimensional reconstruction were performed. Intraoperative O-arm navigation system three-dimensional reconstruction and triplane scanning imaging were used to evaluate the effect of intraoperative reduction. The anterior pelvic ring was fixed with internal external fixator, and the posterior ring was fixed with sacroiliac screw, plate screw or lumbar iliac screw. The operation time, intraoperative bleeding and nail placement were observed and recorded. The quality of fracture reduction was evaluated by Matta standard, and the postoperative function was evaluated by Majeed function score.@*RESULTS@#Wound healing was good in all patients without vascular, nerve and local irritation complications. All the 15 patients were followed up for 10 to 16 months. The fracture reduction was evaluated according to the Matta scoring standard, 9 cases were excellent results, 5 cases were good, and 1 case was medium. The Majeed functional score was 0 to 95 points.@*CONCLUSION@#The built-in external fixator assisted O-arm navigation imaging system in the treatment of unstable pelvic fractures. The reduction effect is evaluated in advance, the operation time is shortened, and the accuracy of internal fixation is improved. The operation is simple, safe and less bleeding. The operation is in line with the principles of minimally invasive medical treatment and precision medical treatment in orthopedics, which is conducive to the recovery of patients' postoperative function and rapid recovery.

Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics / 中国中药杂志

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

Metabolic engineering study on biosynthesis of 4-hydroxybenzyl alcohol from L-tyrosine in Escherichia coli / 中国中药杂志

As an important active ingredient in the rare Chinese herb Gastrodiae Rhizoma and also the main precursor for gastrodin biosynthesis, 4-hydroxybenzyl alcohol has multiple pharmacological activities such as anti-inflammation, anti-tumor, and anti-cerebral ischemia. The pharmaceutical products with 4-hydroxybenzyl alcohol as the main component have been increasingly favored. At present, 4-hydroxybenzyl alcohol is mainly obtained by natural extraction and chemical synthesis, both of which, however, exhibit some shortcomings that limit the long-term application of 4-hydroxybenzyl alcohol. The wild and cultivated Gastrodia elata resources are limited. The chemical synthesis requires many steps, long time, and harsh reaction conditions. Besides, the resulting by-products are massive and three reaction wastes are difficult to treat. Therefore, how to artificially prepare 4-hydroxybenzyl alcohol with high yield and purity has become an urgent problem facing the medical researchers. Guided by the theory of microbial metabolic engineering, this study employed the genetic engineering technologies to introduce three genes ThiH, pchF and pchC into Escherichia coli for synthesizing 4-hydroxybenzyl alcohol with L-tyrosine. And the fermentation conditions of engineering strain for producing 4-hydroxybenzyl alcohol in shake flask were also discussed. The experimental results showed that under the conditions of 0.5 mmol·L~(-1) IPTG, 15 ℃ induction temperature, and 40 ℃ transformation temperature, M9 Y medium containing 200 mg·L~(-1) L-tyrosine could be transformed into(69±5)mg·L~(-1) 4-hydroxybenzyl alcohol, which has laid a foundation for producing 4-hydroxybenzyl alcohol economically and efficiently by further expanding the fermentation scale in the future.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Parkinson's Disease in Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a neurodegenerative disease that seriously endangers the health of the middle-aged and elderly people. The main clinical manifestations include motor symptoms such as bradykinesia， static tremor， and myotonia and non-motor symptoms like constipation， mental disorders， sleep disorders， and autonomic nervous dysfunction. Its etiology and pathogenesis have not been fully understood， and the clinical efficacy is not satisfactory. By searching the relevant literature in China and abroad in recent years， this paper summarized the etiology， pathogenesis， and treatment of PD in both traditional Chinese medicine （TCM） and western medicine as well as the integrated TCM and Western medicine treatment. In general， liver and kidney deficiency is recognized by domestic experts in related fields as the main pathogenesis of PD. The abnormal aggregation of α-synuclein， oxidative stress， mitochondrial dysfunction， ubiquitin-proteasome system dysfunction， neuroinflammation， autophagy， microbiota-gut-brain axis regulation， and excitatory neurotoxicity are closely related to the pathogenesis of this disease. At present， treatment based on syndrome differentiation， empirical formulae from famous doctors， single Chinese herbs， and acupuncture and moxibustion are mainly adopted for the tackling of PD in TCM. Western medicine is still dominated by drug replacement therapy， supplemented by such surgical treatments as traditional immunotherapy， neurotrophic factors， and deep brain stimulation （DBS）， rehabilitation and exercise therapy， and scientific nursing. Gene therapy has become a new technical means for the treatment of this disease in recent years. In addition， the combined therapy of TCM and Western medicine has received increasing importance. This paper reviewed the pathogenesis and treatment of PD in TCM and Western medicine， so as to provide reference for its clinical diagnosis and treatment.

Jinxiangdan Inhibits NLRP3/IL-1β/Caspase-1 Pathway to Alleviate Myocardial Ischemia-reperfusion Injury in Rats / 中国实验方剂学杂志

Objective:To observe the effect of Jinxiangdan （JXD） on NOD-like receptor pyrin domain-containing-3 （NLRP3）/cysteine-dependent aspartate-directed protease-1 （Caspase-1）/interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） signaling pathway in myocardium of rats with myocardial ischemia-reperfusion injury （MIRI） and explore the protective effect and mechanism of JXD against MIRI. Method:Fifty male SD rats were randomly divided into the sham operation group， model group， high- and low-dose JXD groups， and positive drug （Di'ao Xinxuekang） group， with 10 rats in each group. Seven days before modeling， rats in the JXD groups were separately treated with intragastric administration of 0.72 and 0.18 g·kg^-1 JXD tablets， the ones in the sham operation group and model group with the same volume of normal saline， and those in the positive drug group with 1.29 g·kg^-1 Di'ao Xinxuekang. Twelve hours after the last intragastric administration， the anterior descending branch of the left coronary artery was ligated for 30 min and then re-perfused for 60 min for inducing MIRI. ST segment elevation was detected by electrocardiogram（ECG） for model evaluation. The contents of creatine kinase （CK） and lactate dehydrogenase （LDH） in cardiac tissue were measured by colorimetry. Hematoxylin-eosin （HE） staining was conducted for observing myocardial histopathological changes， followed by the detection of cardiomyocyte apoptosis by DNA in situ nick end-labeling （TUNEL） assay. The protein and mRNA expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> were detected by Western blot and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:Compared with sham operation group， the model group exhibited obviously elevated ST segment （<italic>P</italic><0.01）， enhanced CK and LDH activities in the myocardium （<italic>P</italic><0.01）， increased apoptotic cardiomyocytes （<italic>P</italic><0.01）， and up-regulated NLRP3， Caspase-1， and IL-1<italic>β</italic> protein and mRNA expression （<italic>P</italic><0.01）. Compared with model group， JXD at both the high and low doses and Di'ao Xinxuekang significantly lowered the ST segment （<italic>P</italic><0.05，<italic>P</italic><0.01）， diminished the CK and LDH activities in myocardial tissue （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved the apoptosis of cardiomyocytes （<italic>P</italic><0.05，<italic>P</italic><0.01）， and down-regulated the mRNA and protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> in myocardial tissue （<italic>P</italic><0.05，<italic>P</italic><0.01）. The ST segment of ECG in the low-dose JXD group was increased as compared with that in the Di'ao Xinxuekang group （<italic>P</italic><0.05）， while the ST segment in the high-dose JXD group was obviously elevated （<italic>P</italic><0.05）. Besides， the green fluorescence intensities in the low- and high-dose JXD groups and the Di'ao Xinxuekang group remarkably declined （<italic>P</italic><0.05，<italic>P</italic><0.01）. The mRNA and protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> in the high-dose JXD group were down-regulated （<italic>P</italic><0.05）. Conclusion:JXD alleviates MIRI possibly by lowering NLRP3 and IL-1<italic>β</italic> expression and inhibiting cardiomyocyte apoptosis.

Neurological Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years， the incidence of neurological diseases has been increasing year by year. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of neurological disorders， identify the breakthrough point of integrating TCM with western medicine， and further standardize the clinical diagnosis and treatment of TCM， the China Association of Chinese Medicine organized neurologists in TCM and western medicine to carry out in-depth discussion on the neurological diseases responding specifically to TCM and integrated TCM and western medicine， such as stroke， headache， vertigo， multiple sclerosis， and epilepsy， aiming to formulate a well-recognized and integrated treatment protocol for TCM and western medicine and improve the efficacy of neurological disorders. Furthermore， the treatment suggestions of the corresponding diseases in TCM and western medicine were proposed to provide references for clinical practice and scientific research.

Preparation and in vitro evaluation of vitamin K1-loaded erythrocyte drug delivery system / 国际药学研究杂志

Objective: To establish a vitamin K1(VK1)-delivery system with red blood cells as carrier. Methods: The VK1 self-emulsifying nano-emulsion, micelle and plasma solution were prepared to investigate the VK1 loading on red blood cells. The VK1- chitosan(CS)nanoparticles were prepared with different particle size by the 3 different preparation methods, and the effect of the particle size and charge property on the VK1-loading on red blood cells was investigated with the prepared VK1-CS nanoparticles. The encapsulation efficiency and drug loading were used as main indicators to investigate the appropriate drug loading method. Results: Due to the solubility of VK1 or the charge properties of nanoparticles, the drug loading and encapsulation efficiency of the red blood cell-encapsulated VK1 were quite low, and a large amount of drugs could not be loaded on the red blood cells. The ability of red blood cells to load VK1 was likely related to its Zeta potential. The VK1-CS nanoparticles prepared by the ion condensation method showed a good drug loading performance. Each milliliter of red blood cells could load 174.46 μg VK1 in the nanoparticles, and the loading rate was 85.11%. Conclusion: The VK1 loading by the red blood cells could be achieved by the electrostatic interaction between the positively charged chitosan nanoparticles and the negatively charged erythrocyte membrane.

Efficacy and Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Monocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute monocytic leukemia (AML-M5) and the related factors that affecting the prognosis of the patients.@*METHODS@#The clinical data of 71 patients with AML-M5 treated with allo-HSCT in Zhujiang Hospital Affiliated to Southern Medical University from April 2009 to October 2019 were collected and retrospectively analyzed. The incidence of graft-versus-host disease (GVHD), cumulative overall survival (OS) rate, cumulative progression-free survival (PFS) rate, transplantation-related mortality (TRM), relapse rate and the risk factors affecting prognosis in the patients were analyzed.@*RESULTS@#66 patients obtained hematopoietic reconstruction after transplantation, the median time of granulocyte implantation was 12 (9-26) d, and the median time of megakaryocytic implantation was 13 (8-72) d. The incidence of acute GVHD and chronic GVHD was 33.8% (24/71) and 36.6% (26/71), respectively. The median follow-up time was 13.81 (0.16 to 112.54) months; the median OS and PFS was 31.27 and 26.07 months, respectively. The cumulative OS of the patients in 1 and 3 years after transplantation was 64.9% and 48.6%, respectively, and the cumulative PFS of the patients in 1 and 3 years was 55.0% and 39.5%, respectively. The cumulative relapse rate of the patients in 1 and 3 years was 24% and 40%, respectively. Multivariate analysis showed that pre-transplantation relapse was the independent risk factor affecting OS (HR=2.32, 95%CI:1.17-4.62, P=0.02) and PFS (HR=3.08, 95%CI:1.61-5.90, P=0.001) of the patients; invasive fungal disease after transplantation was the independent risk factor affecting OS (HR=2.71, 95% CI:1.32-5.56, P=0.007) and PFS (HR=2.87, 95%CI=1.40-5.86, P=0.004) of the patients; FLT3 mutation was the independent risk factor affecting PFS (HR=2.13, 95%CI=1.07-4.24, P=0.03) of the patients.@*CONCLUSION@#AML-M5 is the intermediate or high-risk leukemia, and allo-HSCT can improve the survival prognosis of the patients. Pre-transplantation relapse and invasive fungal disease after transplantation are the important factors affecting the efficacy of allo-HSCT in patients with AML-M5.

Role and Mechanism of Ski in Glial Scar Formation post Spinal Cord Injury (review) / 中国康复理论与实践

Ski is an evolutionary conserved protein, which is involved in diverse cellular processes such as proliferation, differentiation, transformation and tumor progression. In spinal cord injury, the activation of astrocytes and reactive astrocyte hyperplasia are important factors affecting the formation of glial scar after spinal cord injury. Ski is highly expressed after spinal cord injury, and acts on astrocytes through transforming growth factor-beta, mitogen-activated protein kinase and other signaling pathways, and regulates their activation, proliferation, migration and glial scar formation, providing a new therapeutic direction for the treatment of spinal cord injury.

Advance of Botulinum Toxin A in Neurological Disorders (review) / 中国康复理论与实践

The studies of Botulinum toxin A (BoNT/A) are progressing in many fields. BoNT/A has been used in neurological disorders, such as pains, spasticity, dystonias and autonomic disorders, etc. The pharmacological interaction among BoNT/A, neuronal transport and protein has been explored, and promoted basic science studies.

Effects of Ramipril on the expression of connexin 43 in cerebral arteries of spontaneously hypertensive rats / 生理学报

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.

Effects of Acupuncture on Alzheimer's Disease: Evidence from Neuroimaging Studies / 中国结合医学杂志

As the worldwide population ages, the prevalence of Alzheimer's disease (AD) increases. However, the results of promising medications have been unsatisfactory. Chinese acupuncture has a long history of treating dementia, but lack of evidence from well-designed randomized controlled trials that validate its efficacy and safety, as well as its lack of clear underlying mechanisms, contribute to its limited application in clinical practice. In recent years, brain imaging technologies, such as functional magnetic resonance imaging and positron emission tomography, have been used to assess brain responses to acupuncture in a dynamic, visual, and objective way. These techniques are frequently used to explore neurological mechanisms of responses to acupuncture in AD and provide neuroimaging evidence as well as starting points to elucidate the possible mechanisms. This review summarizes the existing brain imaging evidence that explains the effects of acupuncture for AD and analyzes brain responses to acupuncture at cognitive-related acupoints [Baihui (GV 20), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), and Taixi (KI 3)] from perspectives of acupoint specificity and acupoint combinations. Key issues and directions to consider in future studies are also put forward. This review should deepen our understanding of how brain imaging studies can be used to explore the underlying mechanisms of acupuncture in AD.

Significance and expression of aquaporin-2 in fetus kidney and amniotic fluid at different stages of the pregnancy / 中华实用儿科临床杂志

Objective To explore the expression of aquaporin-2 (AQP-2) in human fetus kidney and amniotic fluid at different stages of pregnancy.Methods Twenty-two cases of aborted fetuses' kidneys were collected.They were divided into 3 groups according to the pregnancy age:8 cases in 17-23 + 6 weeks,8 cases in 24-31 +6 weeks,and 6 cases in 32-38 +6 weeks.Western blot was used to examine the expression of AQP-2 in the kidney.Twenty-four cases of the amniotic fluid were collected,and they were divided into 3 groups according to the pregnancy age:10 cases in 17-23 +6 weeks,6 cases in 24-31 +6 weeks,and 8 cases in 32-38 +6 weeks.Eight cases of healthy adult morning urine were collected as positive controls.The AQP-2 protein in the amniotic fluid was detected with the method of enzyme-linked immunosorbent assay (ELISA) and the osmotic pressure of amniotic fluid at different stages of the pregnancy was measured with the freezing point osmometer.Results The expression of AQP-2 was increased with the extending of pregnancy age,and the AQP-2 expressions in fetus kidney of 17-23 +6 weeks,24-31 + 6 weeks and 32-38 +6 weeks were 0.986 ± 0.335,1.566 ± 0.272,and 2.080 ± 0.246,respectively,and the difference was significant (P ＜ 0.05).The AQP-2 detected from amniotic fluid was positively correlated with the result of AQP-2 in the kidney(r =0.985,P ＜ 0.05),and the AQP-2 expression also increased with the extending of pregnancy age:17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks and adult urine was (30.253 ±5.843) mg/L,(35.103 ±7.271) mg/L,and (42.580 ± 1.230) mg/L and (46.493 ± 0.450) mg/L,respectively.The osmolality of the amniotic fluid of 17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks was (272.600 ± 4.827) mmol/L,(252.00 ± 15.360) mmol/L,and (261.750 ±5.560) mmol/L,respectively,and the difference was significant(P ＜0.05).Conclusions The AQP-2 expression in human fetus kidneys has good correlation with amniotic fluid,which indicates that the level of AQP-2 of the amniotic fluid may reflect the expression of AQP-2 in the fetus kidney.