Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Effect of intravitreal injection of anti-vascular endothelial growth factor agents on systemic concentration of vascular endothelial growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

Effect of perioperative clinical application of enhanced recovery after surgery on elderly recipients undergoing liver transplantation / 器官移植

Objective To evaluate the application value of perioperative interventional strategy guided by enhanced recovery after surgery (ERAS) in elderly recipients undergoing liver transplantation. Methods Clinical data of 405 liver transplant recipients were retrospectively analyzed. According to age, all recipients were divided into the elderly (≥60 years, n=122) and non-elderly groups (< 60 years, n=283). All patients received perioperative interventions under the guidance of ERAS. Intraoperative and postoperative indexes, incidence of postoperative complications and discharge were analyzed between two groups. Results There were no significant differences in the duration of anesthesia, operation time, anhepatic phase, hemorrhage volume, blood transfusion volume, lactic acid level before abdominal closure, ventilator-assisted time, the length of intensive care unit (ICU) stay, Caprini score, CHIPPS score, time of gastric tube, urinary tube and drainage tube removal, time to first drinking, time to first physical activity and time to first flatus between two groups (all P > 0.05). In the elderly group, the time to first feeding was later than that in the non-elderly group (P < 0.05). There were no significant differences in the incidence of fever, ascites, pulmonary infection, delayed gastric emptying, hemorrhage and inactive venous thrombosis between two groups (all P > 0.05). No significant differences were observed in the levels of aspartate aminotransferase, total bilirubin, direct bilirubin, serum creatinine before discharge and total length of hospital stay between two groups (all P > 0.05). The alanine aminotransferase level in elderly recipients was lower than that in non-elderly counterparts, and the difference was statistically significant (P < 0.05). No unplanned reoperation was performed within postoperative 30 d in two groups. There was no significant difference in the re-hospitalization rate within 30 d after discharge (P > 0.05). Conclusions ERAS-guided interventional strategy contributes to perioperative recovery of elderly recipients undergoing liver transplantation, and yields equivalent postoperative recovery between elderly and non-elderly recipients.

Cathayanalactone G and other constituents from leaves and twigs of Callicarpa cathayana / 中草药·英文版

Objective: To study the chemical constituents from the leaves and twigs of Callicarpa cathayana. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel, MCI gel CHP 20P/P120, Sephadex LH-20, and HPLC. The structures of the compounds were determined by HR-ESI-MS, 1D and 2D NMR data. Results: A total of 24 compounds were isolated from the 85% methanol extract of leaves and twigs of C. cathayana. They were identified as cathayanalactone G (1), a new diterpene, and 23 known compounds as patagonic acid (2), (-)-16-hydroxycledroda-3,13-dien-16,15-olide-18-oic acid (3), 15-methoxypatagonic acid (4), oleanolic acid (5), ursolic acid (6), siaresinolic acid (7), pomolic acid (8), α-amyrin (9), tormentic acid (10), lupeol (11), 5,7-dihydroxy-3,4′-dimethoxyflavone (12), 5,4′-dihydroxy-3,7,3′-dimethoxyfla-vone (13), 5-hydroxy-3,6,7,4′- tetramethoxyflavone (14), salvigenin (15), kaemferol (16), astragalin (17), pinoresinol 4-O-β-D-glucopyranoside (18), paulownin (19), β-sitosterol (20), β-sitosterol β-D-glucopyranoside (21), 5-hydroxy-coumarin (22), isocopoletin (23), and 4-hydroxycinnamic acid (24). Conclusion: Compound 1 is a new labdane diterpene. Compounds 10, 13, 16 and 17 are isolated from the genus Callicarpa for the first time. Compounds 7, 8, 9, 12, 14, 23 and 24 are reported from C. cathayana for the first time.

Research progress on the regulation and mechanism of reactive oxygen species on tumor immune checkpoints / 药学学报

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine / 中西医结合学报

In recent years, new preparations of traditional Chinese medicines (TCMs) have been developed, increasing the need for their clinical trials. Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs, as the therapeutic effects of the tested TCMs can be more properly judged. The basic attributes of TCM placeboes include similarity, safety, applicability and controllability. In particular, it is necessary to have similarities in appearance, color, smell and taste between the tested TCMs and placeboes. This is quite difficult for some TCMs due to their distinctive smell and taste. On the other hand, according to the TCM theory on homology of medicine and food, many foods also have certain bioactivities, potentially further complicating the selection of materials for TCM placeboes. In this review, firstly, studies on the special smell and taste of TCMs were introduced. Then, the preparation quality evaluation processes for TCM placeboes were summarized and discussed, based on the relevant literature published in recent years and the research results from our own lab. This review will facilitate the further research and development of TCM placeboes.

A new benzaldehyde from the coral-derived fungus Aspergillus terreus C23-3 and its anti-inflammatory effects via suppression of MAPK signaling pathway in RAW264.7 cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.

Exploration and Application of ESB High-availability Architecture Construction Based on Hospital Information System / 中国医疗器械杂志

OBJECTIVE@#To solve the ESB bus performance and safety problems caused by the explosive growth of the hospital's business, and to ensure the stable interaction of the hospital's business system.@*METHODS@#Taking the construction of our hospital's information system as an example, we used AlwaysOn, load balancing and other technologies to optimize the ESB bus architecture to achieve high availability and scalability of the hospital's ESB bus.@*RESULTS@#The ESB bus high-availability architecture effectively eliminates multiple points of failure. Compared with the traditional dual-machine Cluster solution, the security is significantly improved. The nodes based on load balancing can be scaled horizontally according to the growth of the hospital's business volume.@*CONCLUSIONS@#The construction of the ESB bus high-availability architecture effectively solves the performance and security issues caused by business growth, and provides practical experience for medical information colleagues. It has certain guiding significance for the development of regional medical information.

Design and Verification of Human Metabolic Measurement System Based on STM32 / 中国医疗器械杂志

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Accuracy and safety of robot assisted pedicle screw placement / 中国骨伤

OBJECTIVE@#To investigate the accuracy and safety of pedicle screw placement assisted by orthopedic robot and C-arm fluoroscopy.@*METHODS@#The clinical data of 36 patients with spinal diseases underwent surgical treatment from January 2019 to August 2020 was retrospectively analyzed. Among them, 18 cases were implanted pedicle screws assisted by orthopaedic robot(observation group), including 12 males and 6 females, aged from 16 to 61 years with an average of (38.44±3.60) years;there were 1 case of adolescent scoliosis, 1 case of spinal tuberculosis, 7 cases of lumbar spondylolisthesis, 4 cases of thoracic fracture and 5 cases of lumbar fracture. Another 18 cases were implanted pedicle screws assisted by C-arm fluoroscopy(control group), including 10 males and 8 females, aged from 18 to 58 years with an average of (43.22±2.53) years;there were 1 case of adolescent scoliosis, 6 cases of lumbar spondylolisthesis, 6 cases of thoracic fracture and 5 cases of lumbar fracture. The intraoperative fluoroscopy times, nail placement time and postoperative complications were recorded in two groups. CT scan was performed after operation. The Gertzbein-Robbins standard was used to evaluate the accuracy of pedicle screw placement which was calculated.@*RESULTS@#The number of intraoperative fluoroscopy in observation group was(6.89±0.20) times, which was significantly higher than that in control group(14.00±0.18)times(P<0.05). The placement time of each screw in observation group was(2.56±0.12) min, which was significantly different from that in control group(4.22±0.17) min (P<0.05). One case of incision infection occurred in control group after operation, and recovered after active dressing change. During the follow-up period, no serious complications such as screw loosening and fracture occurred in two groups, and there was no significant difference in complications between two groups(P>0.05). A total of 107 screws were placed in observation group, including 101 screws in class A, 4 in class B, 2 in class C, 0 in class D and 0 in class E, the accuracy rate of pedicle screw placement=[(number of screws in class A+B) / the number of all screws placed in the group] ×100%=98.1%(105/107); and a total of 104 screws were placed in control group, including 90 screws in class A, 4 in class B, 5 in class C, 5 in class D and 0 in class E, the accuracy rate of pedicle screw implantation=[(number of screws in class A+B/the number of all screws placed in the group]×100%=90.3% (94/104); there was significant difference between two groups (P<0.05).@*CONCLUSION@#Orthopaedic robot assisted pedicle screw placement has the advantages of less fluoroscopy times, shorter screw placement time and higher accuracy, which can further improve the surgical safety and has a broad application prospect in the orthopaedic.

Analysis of CiteSpace knowledge map for traditional Chinese medicine prevention and treatment of cerebral small vessel diseases / 中国中药杂志

This study aims to analyze the research on the prevention and treatment of cerebral small vessel diseases(CSVDs) with traditional Chinese medicine(TCM) based on knowledge map, and to preliminarily explore the research hotspots and trends. To be specific, articles on TCM treatment of CSVDs in CNKI, Wanfang, and VIP(from establishment to November 2021) were retrieved, followed by bibliometric analysis. Then CiteSpace 5.7 R4 and Gephi were employed for generation of maps on annual number of articles, author cooperation, institution cooperation, keyword co-occurrence, keyword clustering, and keyword emergence. A total of 106 eligible articles were screened out, and the annual number of articles presented a steady upward trend. A total of 277 authors were included in the author cooperation network, among whom CHEN Zhigang published the most articles. A total of 87 institutions were included in the institution cooperation network, among which Dongfang Hospital of Beijing University of Chinese Medicine showed the most frequent cooperation with other institutions. Keyword clustering showed that research on the TCM treatment of CSVDs mainly focused on five aspects: related disease research, neurological function deficits, disease nature and location in TCM, TCM treatment methods, and formulas. The prevention and treatment of CSVDs with TCM in China has been developing steadily in the past ten years, and TCM has unique advantages in the prevention and treatment of this disease. The knowledge maps vividly demonstrated the development and research hotspots and trends in this field. The result is expected to provide a reference for further research in this field.

Exploration and reflection on evaluation methodology of human use experience for new Chinese drug development / 中国中药杂志

The "triple combination" review system provides an opportunity for the transformation of human use experience into new Chinese drugs. However, there are some methodological and technical limitations in the assessment of human experience. Hence, the efficacy and safety evaluation methods should be established in accordance with the characteristics of Chinese herbs. This study summarized some evidence-based methodology to promote the transformation of human use experience to new Chinese drugs, mainly including the individualized pragmatic randomized controlled trial(RCT), cluster RCT, single-case RCT, single arm RCT with objective performance criteria, and partially nested RCT. As the real world data can be used to support the transformation of human experience, attention should be paid to convenient and efficient collection of data, prudent selection of design types, and adoption of appropriate ana-lysis methods to deal with confounding bias, including multi-factor regression model and propensity score. The newly proposed mixed research method can also be utilized to assess the human use experience, which is suitable for mining the theory of traditional Chinese medicine(TCM) and expert experience from different aspects. Meanwhile, considering the study design requirements and TCM cha-racteristics, this study put forward the common problems and solutions in the development of new Chinese drugs based on human use experience, including how to select the feasible outcome indicators, how to collect prescription data in the case of herb and dosage adjustment, and how to evaluate the comprehensive effectiveness of TCM from the perspective of "combination of disease and syndrome".

Molecular mechanism of astragaloside Ⅳ against atherosclerosis by regulating miR-17-5p and PCSK9/VLDLR signal pathway / 中国中药杂志

This study explores the regulatory effect of astragaloside Ⅳ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside Ⅳ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside Ⅳ-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside Ⅳ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside Ⅳ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group. In summary, astragaloside Ⅳ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.

Application and significance of mixed methods research in traditional Chinese medicine and narrative medicine / 中国中药杂志

Since narrative medicine was introduced in China, it has been widely used in medical education and clinical practice. The research on narrative medicine in China is especially characterized by its combination with traditional Chinese medicine(TCM). At present, the research on narrative medicine in China is still in the stage of small-scale practicing and theory advocating. Besides, there is also a lack of guidance on experimental design methodology for clinical application, which leads to few high-quality studies in this field. The present study reviewed the current high-quality research on narrative medicine to discuss the value and prospects of mixed methods research in narrative medicine. In addition, the common design, application procedures, and notes of mixed methods research were explained to provide references for the extensive applications of narrative medicine in the medical field, especially TCM clinical practice, education, and scientific research.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Clinical observation of Tiaoshen acpuncture for dry eye syndrome with yin deficiency of liver and kidney / 中国针灸

OBJECTIVE@#To compare the curative effect of Tiaoshen acupuncture combined with artificial tears and artificial tears alone for dry eye syndrome with yin deficiency of liver and kidney.@*METHODS@#A total of 70 patients of dry eye syndrome with yin deficiency of liver and kidney were randomized into an acupuncture combined with medication group (35 cases, 2 cases dropped off) and a medication group (35 cases, 3 cases dropped off). In the medication group, 0.1% sodium hyaluronate eye drop was applied, 3 times a day, 1 drop each time. On the basis of the treatment as the medication group, Tiaoshen acupuncture was applied at Shenting (GV 24), Shenmen (HT 7), Benshen (GB 13), Taixi (KI 3), Taichong (LR 3), Guangming (GB 37), Fengchi (GB 20), Tongziliao (GB 1), Yuyao (EX-HN 4) in the acupuncture combined with medication group, Tongziliao (GB 1) and Yuyao (EX-HN 4) were connect with electroacupuncture, the needles were retained for 30 min, once a day, 6 times a week. Both groups were treated for 2 weeks. Before and after treatment, the clinical symptom score, SchirmerⅠtest (SⅠT), break-up time (BUT), corneal fluorescein staining (FL) score and Hamilton anxiety scale (HAMA) score were observed in the two groups, and the clinical efficacy was compared in the two groups.@*RESULTS@#Compared before treatment, the clinical symptom scores, corneal FL and HAMA scores were decreased (P<0.05), the levels of SⅠT and BUT were increased after treatment in the two groups (P<0.05). After the treatment, the clinical symptom score, FL and HAMA scores in the acupuncture combined with medication group were lower than the medication group (P<0.05), the levels of SⅠT and BUT in the acupuncture combined with medication group were higher than the medication group (P<0.05). The total effective rate in the acupuncture combined with medication group was 90.9% (30/33), which was higher than 71.9% (23/32) in the medication group (P<0.05).@*CONCLUSION@#Tiaoshen acupuncture combined with artificial tears could promote the secretion of tears for patients of dry eye syndrome with yin deficiency of liver and kidney, repair corneal defect and prolong tear film break-up time, and alleviate anxiety state, its curative effect is better than simple artificial tears.

Effect of human umbilical cord derived mesenchymal stem cells on apoptosis of rat retinal ganglion cells under high glucose and on the regulation of p38MAPK pathway / 中华实验眼科杂志

Objective:To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on the apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR) model rats and on the regulation of p38 mitogen-activated protein kinase (p38MAPK) pathway.Methods:Forty-five SPF male 8-week old SD rats were selected.The DR rat model was established by intraperitoneal injection of streptozotocin (STZ) combined with a high-sugar and high-fat diet.The fasting blood glucose (FBG) and body weight of the rats were measured every week during the high-sugar and high-fat diet, and fundus angiography was used to observe the circulation and leakage of retinal blood vessels.Forty rats with successful modeling were randomly divided into model group and hUC-MSC injection group according to the random number table method, with 20 rats in each group.Another 20 normal rats fed routinely were served as control group, and intraperitoneally injected with the same amount of citric acid buffer.The hUC-MSC injection group was injected intravitreously with hUC-MSC, and the control group and model group were injected intravitreously with the same amount of phosphate buffer saline (PBS). Fluoro gold (FG) retrograde tracer labeling RGCs was used to observe the number of survived RGCs.Hematoxylin-eosin staining was used to observe the pathological changes of retina.TUNEL method was used to observe the apoptosis of RGCs.Western blot was used to detect B cell lymphoma /leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), p38MAPK and phosphorylated (p-) p38MAPK protein expression in retinal tissues.The use and care of the rats complied with the ARVO statement.The study protocol was approved by an Animal Ethics Committee of Zhengzhou central Hospital Affiliated to Zhengzhou University (NO.2980316).Results:The FBG of control rats was maintained at a normal level, and the body weight gradually increased over time, and was gradually decreased as the course of disease prolonged.The retinal blood vessels ran normally without fluorescein leakage in the control group.In the modeling group, the FBG was maintained at a high level, and the body weight increased slowly and gradually decreased with the prolongation of the disease course since the second week after modeling.The distal retinal vessels were found twisted with large area of capillary fluorescein leakage in the modeling group.The density of RGCs in the control group, model group and hUC-MSC injection group were (2 136.10±215.17), (849.40±167.82), (1 549.20±183.26) cells/mm 2, with significant overall differences ( F=115.218, P<0.01). The density of RGCs in the model group and the hUC-MSC injection group were significantly lower than that of the control group, and the density of RGCs in the hUC-MSC injection group was significantly higher than that of the model group, and the differences were statistically significant (all at P<0.05). The retina in the control group was with clear structure, distinct layers, and a large number of complete RGCs.The number of RGCs in the model group was significantly reduced with nuclear pyknosis, thinned and atrophied RGC layer.The retinal structure was relatively complete, and there were more RGCs in the hUC-MSC injection group than the model group.The apoptosis rates of RGCs in the control group, model group and hUC-MSC injection group were (2.16±1.11)%, (43.47±2.26)%, (20.75±2.18)%, with significant overall difference ( F=445.159, P<0.01). The apoptosis rates of RGCs in the model group and hUC-MSC injection group were significantly higher than that of the control group, and the apoptosis rate of RGCs in the hUC-MSC injection group was lower than that of the model group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of Bax, Bcl-2 and p-p38MAPK proteins in the retina tissues among the three groups ( F=30.982, 12.526, 73.158, all at P<0.01). The relative expression of Bax and p-p38MAPK protein were significantly higher, and the relative expression of Bcl-2 protein was significantly lower in the hUC-MSC injection group and the hUC-MSC injection group than those of the control group, and the differences were statistically significant (all at P<0.05). The relative expression of Bax and p-p38MAPK protein was significantly lower, and the relative expression of Bcl-2 protein was significantly higher in the hUC-MSC injection group than those in the model group, and the differences were statistically significant (all at P<0.05). There was no significant difference in the relative expression of p38MAPK protein among the three groups ( F=1.182, P=0.322). Conclusions:Intravitreal injection of hUC-MSC can inhibit the apoptosis of RGCs in DR model rats and protect the retinal structure of rats, which may play an anti-apoptotic effect by inhibiting the p38MAPK signaling pathway.

Effect of neutrophil-lymphocyte ratio at the initial visit on the survival of children with newly diagnosed medulloblastoma / 中华实用儿科临床杂志

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

Clinical feature analysis of medulloblastoma with extraneural metastasis in children / 中华实用儿科临床杂志

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Effect of Rhizoma Drynariae total flavonoids on ER-P38/MAPK pathway of memory impaired mice / 国际中医中药杂志

Objective:To study the effect of total flavonoids of Rhizoma Drynariae on learning and memory impairment mice induced by sodium nitrite. Methods:75 mice were divided into blank group, model group, Kangnaoshuai capsule group, Rhizoma Drynariae total flavonoids group and Rhizoma Drynariae total flavonoids+inhibitor group according to the random number table method, with 15 mice in each group. The Kangnaoshui Capsule group was administered with Kangnaoshui Capsule 585 mg/kg, the Rhizoma Drynariae total flavonoids group was administered with the Rhizoma Drynariae total flavonoids 97.5 mg/kg, the Rhizoma Drynariae total flavonoids group and the inhibitor group were administered with the Rhizoma Drynariae total flavonoids by intragastric administration 97.5 mg/kg, and intraperitoneal injection of 0.072 mg/kg ICI182780 for 21 days, once a day. The model was established on the 22nd day. Except for the blank group, the other mice were injected with sodium nitrite intraperitoneally to replicate the mice model with impaired learning and memory capability. The learning and memory capabilit of mice were detected with water maze method, and the estrogen receptor in hippocampus was detected by immunohistochemistry β (estrogen receptor β, ERβ). The expression of ERβ in hippocampus and the expression of phosphorylated P38 (P-P38) and the protein contents of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated death promoter (Bad) and Caspase-3 in the apoptotic system was detected by Western blot. The kit was used to detect MDA,SOD and NO protein content in hippocampus. Results:The latency of Rhizoma Drynariae total flavonoids group was significantly shorter than the model group, the number of crossing platform and the residence time in the target quadrant were significantly increased ( P<0.01); The expression of ERβ Protein in mice hippocampus (0.371 ± 0.010 vs. 0.124 ± 0.009), Bcl-2 protein (1.146 ± 0.028 vs. 0.726 ± 0.016) and the contents of SOD [(153.657 ± 6.385) U/mg vs. (67.719±5.845) U/mg] increased significantly ( P<0.01); The expression of P-P38/P38 protein (0.412 ± 0.043 vs.0.806 ± 0.069), Bad protein (0.421 ± 0.010 vs.0.633 ± 0.010), Caspase-3 protein (0.923 ± 0.042 vs.1.437 ± 0.033), and the content of MDA [(8.669 ± 0.662) nmol/mg vs. (11.772 ± 1.054) nmol/mg] and NO [(4.259 ± 0.225) nmol/mg vs. (10.805 ± 0.415) nmol/mg] decreased significantly ( P<0.01). In addition, ER blocker can antagonize the above recovery and improvement effects of Rhizoma Drynariae total flavonoids group. Conclusion:Rhizoma Drynariae total flavonoids can regulate memory impairment, inhibit neuronal apoptosis and reduce oxidative stress in sodium nitrite model mice through ER-P38/MAPK signal pathway.