Progress on application of PD⁃1／PD⁃L1 monoclonal antibodies in oncotherapy / 中国生物制品学杂志

@#Abstract：Programmed death receptor⁃ 1（PD⁃1）belongs to the family of immunoglobulin B7⁃CD28，which plays an important role in regulating immune response in human body. Since the first PD⁃1／PD⁃ligand 1（PD⁃L1）monoclonal antibody was approved for marketing in China in 2018，the value of PD⁃1／PD⁃L1 immunotherapy in oncotherapy has attracted wide attention. Based on the introduction of the action mechanism of PD⁃1／PD⁃L1 mAbs，this paper reviews the application progress of 8 on ⁃ market PD ⁃ 1／PD ⁃ L1 mAbs in China in oncotherapy from the perspectives of approved indications，clinical trials，usage and dosage，and adverse reactions，in order to provide reference for the rational appli⁃ cation of PD⁃1／PD⁃L1 monoclonal antibodies in clinic.

Wnt1 and Wnt2b immunodetection of the regenerating tail and comparative ultrastructure of tail spinal cord in the Scincella tsinlingensis / Inmunodetección Wnt1 y Wnt2b de la cola en regeneración y ultraestructura comparativa de la médula espinal de la cola en Scincella tsinlingensis

SUMMARY: The Wnt pathway is essential for the initiation of lizard tail regeneration. The regenerated lizard tails exhibit obvious morphological differences compared to the original ones. The expression of Wnt1 and Wnt2b proteins in the regenerating tail of Scincella tsinlingensis was detected by immunohistochemistry and then comparatively analyzed for ultrastructural changes in the original and regenerated spinal cord. The ependymal layer of the original spinal cord was pseudostratified with multiciliated cells and primary monociliated cells, while the cells of the ependymal layer of the regenerated spinal cord were organized in a monolayer with a few biciliated cells. Immunolocalization indicated that Wnt1 and Wnt2b were mainly distributed in the dermis near the original tail stump, spinal cord, and clot-positive migratory cells during Stage I, 0-1 days post-amputation (dpa). Wnt1 and Wnt2b were predominantly detected in the epaxial and hypaxial musculature near the original tail stump, wound epithelium, and spinal cord in the original tail during Stage II, 1-7 dpa. Mesenchymal cells and wound epithelium showed immunostaining during Stage III and IV, 7-15 dpa. The ependymal tubes contained these signaling proteins during Stage V and VI, 20- 30 dpa. Labeling was mainly observed in nearby regenerative blood vessels, ependymal cells, epaxial and hypaxial musculature in the apical epithelial layer (AEC) after 45-160 dpa. These findings indicated that Wnt1 and Wnt2b proteins presented primarily in regenerating epidermis and nerve tissues were a critical signal for tail regeneration in S. tsinlingensis.

RESUMEN: La vía Wnt es esencial para el inicio de la regeneración de la cola del lagarto. Las colas de lagarto regeneradas exhiben diferencias morfológicas obvias en comparación con las originales. La expresión de las proteínas Wnt1 y Wnt2b en la cola en regeneración de Scincella tsinlingensis se detectó mediante inmunohistoquímica y luego se analizaron comparativamente los cambios ultraestructurales en la médula espinal original y regenerada. La capa ependimaria de la médula espinal original se pseudoestratificó con células multiciliadas y células monociliadas primarias, mientras que las células de la capa ependimaria de la médula espinal regenerada se organizaron en monocapa con algunas células bicilicadas. La inmunolocalización indicó que Wnt1 y Wnt2b se distribuyeron principalmente en la dermis cerca del muñón de la cola original, la médula espinal y las células migratorias positivas en el coágulo durante la Etapa I, 0-1 días después de la amputación (dpa). Wnt1 y Wnt2b se detectaron predominantemente en la musculatura epaxial e hipaxial cerca del muñón de la cola original, el epitelio de la herida y la médula espinal en la cola original durante la Etapa II, 1-7 dpa. Las células mesenquimales y el epitelio de la herida mostraron inmunomarcaje durante la Etapa III y IV, 7- 15 dpa. Los tubos ependimarios contenían estas proteínas de señalización durante la Etapa V y VI, 20-30 dpa. El marcaje se observó principalmente en vasos sanguíneos regenerativos cercanos, células ependimarias, musculatura epaxial e hipaxial en la capa epitelial apical (AEC) después de 45-160 dpa. Estos hallazgos indicaron que las proteínas Wnt1 y Wnt2b están presentes principalmente en la epidermis en regeneración y en los tejidos nerviosos y eran una señal crítica para la regeneración de la cola en S. tsinlingensis.

Immune checkpoint inhibitors induced pituitary immune-related adverse events: diagnosis and management / 中华肿瘤杂志

Immune checkpoint inhibitors (ICIs) have been used in treating a wide variety of cancers, but they challenge clinicians with a series of special immune related adverse events (irAEs) resulting from activated immune system. Since June 2018, when the first programmed cell death 1 (PD-1) inhibitor, nivolumab, was approved by the National Medical Products Administration (NMPA), abundant experience has been accumulated in coping with irAEs from PD-1 and PD-1 ligand 1 (PD-L1) blockade therapies. In October 2021, the first CTLA-4 inhibitor, ipilimumab, which has a different spectrum of irAEs was also approved by NMPA. The discrepancy in clinical features of pituitary irAEs is obvious between these two types of ICIs. Pituitary irAEs include hypophysitis and hypopituitarism. In this review of latest literature, we have summarized the incidence, possible mechanisms, time of onset, clinical presentations, hormone test, pituitary imaging, treatment strategies and recovery patterns of pituitary irAEs. By referring to domestic and foreign clinical guidelines, we have proposed practical suggestions for screening, diagnosing and treating pituitary irAEs.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

Scar-free wound healing following full-thickness cutaneous wounding in the tail and body of Scincella tsinlingensis / Cicatrización de heridas sin cicatrices luego de heridas cutáneas de espesor total en la cola y el cuerpo de Scincella tsinlingensis

SUMMARY: The cutaneous wounds of trunk and tail healing scar-free or with scar were different in lizard species. Full- thickness cutaneous injuries of tail and body of Scincella tsinlingensis were examined by histomorphological and immunohistochemistrical methods. The results showed that all injuries healed without scarring. The process of the wound healing of S. tsinlingensis involved hemostasis, re-epithelialization, proliferation and remodelling, which also could be further subdivided into six stages. Stage I, 0-2 day post wound (dpw), the blood oozed gradually, no obvious wound contraction, minimal blood loss. Stage II, 2-10 dpw, the wound bed covered by the fibrin clot of blood, tissue fluid and tissue debris. Stage III, 7d-15 dpw, the wrinkled wound epitheliums was gradually stratified, and its surface was keratinized and exfoliated. Stage IV, 10-28 dpw, pigment cells were distributed at the boundary between epidermis and dermis, with few blood vessels and no granulation tissue formation. Stage V, 20-70 dpw, opaque scales covered the wound epithelium with randomly scattered melanophores in the base of the epidermis. Stage VI, 45-135 dpw, the epidermis and dermis restored to the thickness of the original skin. Regenerated scales were similar to scales of the uninjured dermis. The positive immunostaining of matrix metalloproteinases-9, cytokeratin 6, alpha smooth muscle actin, caspase 3 and transforming growth factor-β3 showed the specificity of healing period and different stages, which participated in skin wounds healing of S. tsinlingensis.

RESUMEN: En las diferentes especies de lagartos las heridas cutáneas del tronco y la cola sin cicatrices, o con algún tipo de cicatriz son diversas. En este estudio se examinaron las heridas cutáneas de espesor total de la cola y el cuerpo de Scincella tsinlingensis mediante métodos histomorfológicos e inmunohistoquímicos. Los resultados indicaron que todas las lesiones sanaron sin cicatrices visibles. El proceso de cicatrización de heridas de S. tsinlingensis implicó hemostasia, reepitelización, proliferación y remodelación, que también podrían subdividirse en seis etapas. Etapa I, 0-2 días después de la herida (dph), la sangre filtraba gradualmente, sin contracción evidente de la herida, con pérdida mínima de sangre. Etapa II, 2-10 dph, el lecho de la herida estaba cubierto por el coágulo de sangre, líquido tisular y restos tisulares de fibrina. Etapa III, 7-15 dph, los epitelios de la herida se estratificaron gradualmente y su superficie se queratiniza y exfolia. Etapa IV, 10-28 dph, las células pigmentarias se distribuyeron en el límite entre la epidermis y la dermis, con pocos vasos sanguíneos y sin formación de tejido de granulación. Etapa V, 20-70 dph, escamas opacas cubrieron el epitelio de la herida con melanóforos dispersos al azar en la base de la epidermis. Etapa VI, 45-135 dph, la epidermis y la dermis restauradas al grosor de la piel original. Las escamas regeneradas eran similares a las escamas de la dermis sin herida. La inmunotinción positiva de metaloproteinasas- 9 de matriz, citoqueratina 6, actina de músculo liso alfa, caspasa 3 y factor de crecimiento transformante-β3 mostró la especificidad del período de curación y las diferentes etapas, que participaron en la curación de heridas cutáneas de S. tsinlingensis.

Histology and immunocytochemical localization of glial fibrillary acidic protein in the inner ear of Scincella tsinlingensis / Histología y localización inmunocitoquímica de la proteína ácida fibrilar glial en el oído interno de Scincella tsinlingensis

SUMMARY: The microstructure of inner ear in Scincella tsinlingensis was observed by light microscopy and the expression of glial fibrillary acidic protein (GFAP) in membranous labyrinth among the juvenile age group, subadult age group and adult age group were also detected by methods of immunohistochemistry. The inner ear in S. tsinlingensis resembled those in other Scincid lizards in their anatomy and histology. Large and elongate cochlear duct was slightly bowed or arched laterally. There was no hint of limbic modifications and the limbic lip was absent in cochlear recess. The basilar papilla elongated anteroventrally possessed specialized tectorial sallets. GFAP staining was significantly distributed in supporting cells of the sensory epithelia of cochlear duct, while the utricular macula and canal ampullae showed immunopositive for the GFAP antibody, with weaker staining in the saccular macula. The membranous inner ear of three different age groups revealed the similar pattern of GFAP expression, which suggested that the distribution of supporting cells were independent of age in S. tsinlingensis.

RESUMEN: La microestructura del oído interno en Scincella tsinlingensis fue analizada mediante microscopía óptica y por otra parte, fue cuantificada la expresión de la proteína ácida fibrilar glial (GFAP) en el laberinto membranoso, entre los grupos de edad juvenil, subadulto y adulto, utilizándose métodos inmunohistoquímicos. El oído interno de S. tsinlingensis se asemejaba al de otros lagartos Scincid tanto en su anatomía como en su histología. El conducto coclear mayor estaba ligeramente arqueado o arqueado lateralmente. No había indicios de modificaciones límbicas y no se evidenció el labio en el receso coclear. La papila basilar alargada anteroventralmente poseía sallets tectoriales especializados. La tinción de GFAP se distribuyó significativamente en las células del epitelio sensorial del conducto coclear, mientras que la mácula utricular y la ampolla del canal mostraron inmunopositividad para el anticuerpo GFAP, con una tinción más débil en la mácula sacular. El oído interno membranoso de los tres grupos de edad diferentes reveló un patrón similar de expresión de GFAP, lo que sugiere que la distribución de las células de soporte son independiente de la edad en S. tsinlingensis.

Associated factors of non-suicidal self-injury behavior in adolescents with depression disorder / 中国学校卫生

Objective@#To explore associated factors of non-suicidal self-injury in adolescents with depression, and to provide a reference for clinical intervention and treatment.@*Methods@#A cross-sectional survey was conducted among 80 adolescents aged 14-18 years with depressive disorder who visited an outpatient clinic in the PLA 904nd Hospital from January 2015 to January 2017. Eysenck Personality Questionnaire(EPQ), Egma Minnenav Bsrdndosnauppforstran (EMBU), non-suicidal self-injury behavior rating scale were used to investigate them.@*Results@#Male patients with depression had more non-suicidal self-injury than female patients(76.74% vs. 54.05%), and patients with highly educated mothers had more non-suicidal self-injury(77.78%)(χ 2=4.58, 6.11, P<0.05). Self-injury behavior in patients with internal and external (E) the orientation factor score (5.22±2.82) was lower than the score of the patients without self-injury behavior(8.85±2.93)(t=-5.37, P<0.05), neuroticism (N), while psychoticism (P) and hide(L) score [(14.53±3.94) (5.60±1.58) (12.94±0.54)] were higher than patients without self-injury behavior [(11.55±5.71) (3.13±1.43) (12.09±0.55)](t=2.74, 6.82, 6.31, P<0.05); Factors such as "severe paternal punishment" "paternal excessive interference" "paternal refusal to deny" "maternal refusal to deny" and other factors in patients with non-suicidal self-injury [(21.57±4.65) (21.73±4.38) (14.25±5.08) (20.34±4.64)] were all higher than those without nonsuicidal self-injury [(18.50±7.53) (18.77±3.55) (11.58±2.97) (16.55±6.32)](t=2.25, 3.04, 2.96, 3.05, P<0.05); Logistic regression analysis showed that males, mothers with high educational level, and E, N, P (<38.5 and >61.5) were associated with non-suicidal self-injury behavior in adolescents with depression(OR=1.99, 2.31, 1.71, 2.52, 1.98, P<0.05).@*Conclusion@#Gender, maternal education and symptom score were the important factors influencing non-suicidal self-injury.It is necessary to arouse the attention of the family, society and school.

Histomorphology of vomeronasal organ in Scincella tsinlingensis / Histomorfología del órgano vomeronasal en Scincella tsinlingensis

Due to the great change in the morphology of squamate vomeronasal organ (VNO), the histomorphology characteristics of VNO in Scincella tsinlingensis were studied by light and electronic microscopy. The results indicated that the VNO of S. tsinlingensis was located at the base of nasal cavity and consisted of a mushroom body situated anteroventrally and a sensory epithelium (SE) situated dorsocaudally. SE was composed of supporting cells, receptor cells and basal cells, and the supporting cells contained secretory granules near the surface membrane. Most of receptor cells were irregular in shape with long cytoplasmic extensions and characterized by microtubules, vesicles, and mitochondria. The basal cells with long cytoplasmic extensions were also irregular in shape and appeared a greater electron density than others. The thick nerve bundles were found on the dorsomedial area of VNO, and the surface of mushroom body was non-sensory epithelium consisting of ciliated and basal cells, without goblet cells. Epithelial cells were arranged in irregular, with many cilia and microvilli distributed on its free surface. Cells on the basal layer were irregularly circular in shape and arranged sparsely. Taken together, the results indicated that the fine structure of VNO in S. tsinlingensis was similar to other species from scincomorphs.

Debido al gran cambio en la morfología del órgano vomeronasal (OVN), se estudiaron las características histomorfológicas en la Scincella tsinlingensis por microscopías de luz y electrónica. Los resultados indicaron que el OVN de S. tsinlingensis se localizaba en la base de la cavidad nasal y consistía en un cuerpo como hongo situado anteroventralmente y un epitelio sensorial (ES) situado dorso caudamente. El ES estaba compuesto de células de soporte, células receptoras y células basales, y las células de soporte contenían gránulos secretores cerca de la membrana superficial. En gran parte de la mayoría de las células receptoras se observó una forma irregular con largas extensiones citoplasmáticas, caracterizadas por microtúbulos, vesículas y mitocondrias. Las células basales con extensiones citoplasmáticas también tenían forma irregular y algunas parecían tener una mayor densidad de electrones. Los haces gruesos nerviosos se encontraron en el área dorsomedial del OVN, la superficie del cuerpo de estaba compuesto de epitelio no sensorial y consistía de células ciliadas y basales, sin células caliciformes. Las células epiteliales estaban dispuestas de manera irregular, con muchos cilios y microvellosidades distribuidas en su superficie libre. Las células en la capa basal eran escasas y de forma circular irregular. Tomados en conjunto, los resultados indicaron que la estructura fina del OVN en S. tsinlingensis era similar a otras especies de scincomorpha.

Screen of differentially expressed genes in liver cancer xenograft tissues after CDC25Agene silence / 中国肿瘤生物治疗杂志

@#Objective: To explore the genes that may be regulated by cell division cycle 25A (CDC25A) with gene chip technology, and to elucidate and verify that CDC25A has a regulatory effect on the expression of liver cancer related genes. Methods: CDC25A expression in human liver cancer HepG2 cells was silenced by siRNA interference technology and a nude mouse xenograft model of liver cancer was successfully constructed in our previous research. Affymetrix human gene expression profiling microarray was used to further screen differentially expressed genes (DEGs) after silencing CDC25A in liver cancer xenografts, and GO analysis and KEGG analysis were performed. Some of the DEGs were verified by qPCR. Results: The chip screened 188 DEGs in liver cancer xenograft tissues after CDC25A silence, including 78 up-regulated genes and 110 down-regulated genes. These DEGs mainly involved in cell proliferation, apoptosis, protein complex binding, extracellular space, etc., and associated with the changes in pathways such as focal adhesions and extracellular matrix (ECM) receptor interactions. qPCR showed that the expression of HIPK2 mRNA was up-regulated and the mRNA expressions of (microfibrillar-associated protein 5(MFAP5) and cyclin D1 (CCND1) were down-regulated, which were consistent with the results of microarray detection. Conclusion: Using human gene expression profiling chip, the DEGs in liver cancer xenograft tissues in nude mice after silencing CDC25Awere successfully screened, providing effective clues for exploring the effect of CDC25Aon the growth of liver cancer.

Regulatory factors and modulation mechanisms of functions of ovarian germline stem cell niche / 上海交通大学学报（医学版）

With increasing age in women, the ovarian function declines, which leads to decreased follicle generation, declined female fertility and age-related diseases ultimately. Female germline stem cells are epithelial cells existing on the ovarian surface, which can divide into new stem cells symmetrically and differentiate into germ cells and granulosa cells asymmetrically. The discovery of female germline stem cells brings much hope for the post-natal renewal of oocytes and solving female infertility problems. Ovarian germline stem cell niche in which female germline stem cells live is the surrounding microenvironment which plays an essential role in maintaining the function of female germline stem cells. Many factors including nutrition supply, protein, cytokines and signaling pathways can control the biological characters of female germline stem cells, and also influence their proliferation and differentiation. This paper reviewed the knowledge about the influencing factors and regulatory mechanisms of the function of ovarian germline stem cell niche.

Regulatory factors and modulation mechanisms of functions of ovarian germline stem cell niche / 上海交通大学学报（医学版）

With increasing age in women, the ovarian function declines, which leads to decreased follicle generation, declined female fertility and age-related diseases ultimately. Female germline stem cells are epithelial cells existing on the ovarian surface, which can divide into new stem cells symmetrically and differentiate into germ cells and granulosa cells asymmetrically. The discovery of female germline stem cells brings much hope for the post-natal renewal of oocytes and solving female infertility problems. Ovarian germline stem cell niche in which female germline stem cells live is the surrounding microenvironment which plays an essential role in maintaining the function of female germline stem cells. Many factors including nutrition supply, protein, cytokines and signaling pathways can control the biological characters of female germline stem cells, and also influence their proliferation and differentiation. This paper reviewed the knowledge about the influencing factors and regulatory mechanisms of the function of ovarian germline stem cell niche.

Recent Advances in Sensitive Detection of Kinases / 分析化学

Kinases are a class of enZymes that catalyZe the transfer of a phosphate group from a high-energy molecule to their substrates ( i.e., phosphorylation ).Kinase-induced intracellular phosphorylation plays important roles in a variety of cellular processes including metabolism, cell signaling, protein regulation, DNA replication and repair.Consequently, kinases have become potential biomarkers for disease diagnosis and drug discovery, and the development of simple and sensitive methods for kinase assay is highly desirable.In this review, we summariZe the recent advances in kinase assays with protein kinase A (PKA), casein kinase-2 ( CKⅡ) and T4 polynucleotide kinase ( T4 PNK) as the models.We focus on the newly emerging methods for kinase assays including fluorescent, single-molecule detection, colorimetric, chemiluminescent, bioluminescent, and electrochemical and photoelectrochemical methods.Furthermore, we give a new insight into the future direction of kinase assays.

Meta-analysis on Reinhartdt and Sea Capsule combined with Donepezil in treatment of Alzheimer's disease / 药物评价研究

Objective Objective To evaluate the efficacy and safety of Reinhartdt and Sea Capsule (RSC) combined with donepezil (experimental group) compared with donepezil (control group) in treatment of Alzheimer's disease.Methods The randomized controlled trials (RCT) of reinhartdt and sea capsule combine with donepezil in treatment of Alzheimer's disease were searched from Pubmed,VIP,CNKI,CBM,and Wangfang detabase by computer.Deadline from January 2000 to February 2017.References of included studies were also retrieved,extracted data,and assessed the methodological quality.Then,Meta-analysis was performed using RevMan 5.0 software.Results A total of eight RCTs were included,including 605 patients with insomnia.Meta-analysis results showed that compared with control group,experimental group MMSE score [P＜0.001,MD=2.69,95％CI(1.46,3.92)],ADAS-Cog score [P＜0.001,MD=-4.54,95％CI(-5.64,-3.43)] and ADL score [P＜0.001,MD=-3.60,95％CI(-4.53,-2.66)],the difference was statistical;There was no signficant difference between two group in the incidences of adverse effect [P=-0.94,OR=1.02,95％CI(0.63,1.66)].Conclusion RSC combined with donepezil showed better efficacy for Alzheimer's disease,yet without increasing adverse effect rate as compared with donepezil alone.

Effect of grape seed proanthocyanidins on phenotype marker protein of renal cells in db/db mice / 临床与实验病理学杂志

Purpose To investigate the effect of grape seed proanthocyanidins on the phenotype-transforming marker protein expression of db/db renal cells in mice model of type 2 diabetes,and to explore the protective mechanism of grape seed extract on diabetic renal injury in db/db mice.Methods Male db/db diabetic mice were randomly divided into two groups:diabetic group (db/db group) and diabetic + grape seed proanthocyanidin extract group (db/db + GSPE).The same week-old male db/m mice was used as normal controls (db/m) and grape seed proanthocyanidin extract gavage treatment group (db/m +grape seed proanthocyanidin extract group,db/m + GSPE).The mice of db/db + GSPE group and db/m + GSPE group were administered daily with grape seed proanthocyanidin extract (5mg/kg) by gavage.Results Renal tissues of db/db diabetic mice showed increased expression of α-SMA,p-p38MAPK,pERK1/2 and 8-OHdG level,and down-regulation in E-cadherin expression compared with db/m group (P ＜ 0.05).However,the alternations of α-SMA,p-p38,p-ERK1/2,E-cadherin protein levels,and 8-OHdG level,in db/db group were reversed by addition of grape seed proanthocyanidin extract (P ＜ 0.05).Conclusion Grape seed proanthocyanidin extract inhibits the epithelial to mesenchymal transition (EMT) associated protein,by decreasing ROS production,and activating p38 MAPK and ERK1/2.These findings suggest that grape seed proanthocyanidin extract provides a treatment option for diabetic nephropathy.

Research progress on humoral rejection after liver transplantation / 解放军医学杂志

Recent studies have shown that humoral rejection,or antibody-mediated rejection (AMR),is an important risk factor for graft failure.Transplant experts have accumulated some experience on the diagnosis and treatment of AMR after kidney transplantation.However,AMR after liver transplantation has not been fully understood until recently,and its pathogenesis,clinical manifestation,diagnosis and treatment are different from AMR after kidney transplantation.In the research progress,the AMR after liver transplantation was classified into hyper acute rejection,acute humoral rejection,chronic humoral rejection and the state of accommodation.The immunity mechanism of AMR after liver transplantation is also described.The different kinds of AMR after liver transplantation were diagnosed by analyzing the clinical manifestations,serum tests and pathological characteristics of the patients.Moreover,the risk factors of them were mentioned in the article.Then we also introduce the different strategies for prevention and treatment of AMR after liver transplantation.Therefore,based on the current research progress on AMR after liver transplantation,we analyze the future direction of progress.

Impact of Mean Platelet Volume on Prognosis in Patients With ST-segment Elevation Myocardial Infarction / 中国循环杂志

Objective: To evaluate the impact of mean platelet volume (MPV) on prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1012 consecutive STEMI patients received percutaneous coronary intervention (PCI) in our hospital from 2010-01-01 to 2014-10-31 were enrolled. Major adverse cardiovascular events (MACE) were recorded in 2015-10. Based on ROC curve measured optimal critical point of MPV in all-cause death, the patients were divided into Low MPV group and High MPV group. The incidence of MACE was compared between 2 groups, the impact of MPV on prognosis of PCI treated STEMI patients was studied by uni- and multivariate COX regression analysis. Results: By ROC curve, the optimal critical point of MPV in all-cause death was MPV≤9. 466 fl. MPV≤9. 466 fl in Low MPV group, n=549 and MPV>9. 466 fl in High MPV group, n=463. The patients were followed-up for 34 (12-69) months. Compared with Low MPV group, the patients in High MPV group had the higher incidences of all-cause death and cardiac death, P<0. 001 and P=0. 001. With adjusted multivariates, COX regression analysis showed that MPV was an independent risk factor of all-cause death (HR=1. 463, P<0. 001) and cardiac death (HR=1. 458, P<0. 001) in relevant patients. Conclusions: Increased MPV at admission had the predictive value for long-term prognosis in PCI treated STEMI patients.

Meta-analysis on Reinhartdt and Sea Capsule combined with Donepezil in treatment of Alzheimer's disease / 药物评价研究

Objective Objective To evaluate the efficacy and safety of Reinhartdt and Sea Capsule (RSC) combined with donepezil (experimental group) compared with donepezil (control group) in treatment of Alzheimer's disease.Methods The randomized controlled trials (RCT) of reinhartdt and sea capsule combine with donepezil in treatment of Alzheimer's disease were searched from Pubmed,VIP,CNKI,CBM,and Wangfang detabase by computer.Deadline from January 2000 to February 2017.References of included studies were also retrieved,extracted data,and assessed the methodological quality.Then,Meta-analysis was performed using RevMan 5.0 software.Results A total of eight RCTs were included,including 605 patients with insomnia.Meta-analysis results showed that compared with control group,experimental group MMSE score [P＜0.001,MD=2.69,95％CI(1.46,3.92)],ADAS-Cog score [P＜0.001,MD=-4.54,95％CI(-5.64,-3.43)] and ADL score [P＜0.001,MD=-3.60,95％CI(-4.53,-2.66)],the difference was statistical;There was no signficant difference between two group in the incidences of adverse effect [P=-0.94,OR=1.02,95％CI(0.63,1.66)].Conclusion RSC combined with donepezil showed better efficacy for Alzheimer's disease,yet without increasing adverse effect rate as compared with donepezil alone.

A retrospective cohort study on abnormal blood lead levels in lead-exposed workers in a storage battery factory / 中国职业医学

OBJECTIVE: To analyze the influencing factors of high blood lead levels in lead-exposed workers of a storage battery factory. METHODS: By the typical sampling method,lead-exposed workers were chosen as study subjects for a three-year retrospective cohort study starting from September of 2011 and ending in September of 2014. The starting blood lead level was < 400. 0 μg / L and ending blood lead level was ≥400. 0 μg / L( abnormal level). The influencing factors of abnormal blood lead level were analyzed by the COX regression analysis method. RESULTS: There were 244 lead-exposed workers included in this study. The median( M) working years of baseline lead exposure was 6. 3( 0. 7-35. 9) years,the M of baseline blood lead level was 321. 5( 215. 7-398. 7) μg / L by September of 2011. During the 3 years,there were 78 workers found to have abnormal blood lead levels,with an abnormality rate of 32. 0%. The multivariable COX regression analysis indicated that the workers with following situations had relative higher incidences of abnormal blood lead level:working without masks,baseline blood lead level over 300. 0 μg / L,the air concentration of lead in workplace beyond the standard and the workers exposed to lead for over 5. 0 years,their relative risk ratios were 6. 89,4. 00,9. 02 and 2. 93 times of those workers with the opposite situations,respectively( P < 0. 01). CONCLUSION: Measures should be taken to prevent and control the occupational chronic lead poisoning especially in those lead-exposed workers who don't wear masks during work,whose baseline blood lead level was over 300. 0 μg / L,whose air concentrations of lead in workplace were beyond the standard and whose lead exposure year was over 5. 0 years.

A Case of Recurrent Glucocorticoid-Induced Pheochromocytoma Crisisb during the Treatment of Urticaria / 대한내과학회지

Pheochromocytoma crisis is a life-threatening endocrine emergency. Stimuli that can elicit a pheochromocytoma crisis include anesthesia, tumor manipulation, and several drugs. Rarely, glucocorticoids can induce a pheochromocytoma crisis. Here, we describe the case of a 65-year-old female who developed an adrenergic crisis with blood pressure fluctuations, dizziness, and seizures after receiving glucocorticoids for the treatment of urticaria. The symptoms led us to speculate that a pheochromocytoma was present. We confirmed the diagnosis based on abdominal imaging and biochemical studies. The patient's symptoms improved after surgical removal of the pheochromocytoma.

Effect of Bushen Tongdu Capsule on RANK/RANKL/OPG pathway of collagen induced arthritis rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Bushen Tongdu Capsule (BTC) on RANK/RANKL/ OPG pathway of collagen induced arthritis (CIA) rats, thereby laying theoretic evidence for treating rheumatic arthritis (RA) by Chinese medicine.</p><p><b>METHODS</b>RA model was induced by CIA. Totally 42 rats were randomly divided into six groups, i.e., the normal control group, the model group, the low dose BTC (BSL) group, the medium dose BTC (BSM) group, the high dose BTC (BSH) group, and the Tripterygium Glycosides (TG) group, 7 in each group. BTC at the daily dose of 120, 240, and 480 mg/kg was given by gastrogavage to rats in the BSL, BSM, and BSH group respectively from the 13th day of modeling. TG at the daily dose of 24 mg/kg was given by gastrogavage to rats in the TG group. All medication was given once daily, 2 mL each time. Two mL normal saline was administered to rats in the normal control group and the model group. All medication lasted for 18 days. Samples were taken at day 31. The TRAP section of the ankle joint was fixed in 10% formalin for TRAP stain. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) were detected using ELISA.</p><p><b>RESULTS</b>Compared with the normal control group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree were significantly improved in the model group, serum levels of RANKL and M-CSF were up-regulated, levels of OPG and OPG/RANKL were significantly lowered (all P < 0.01). Compared with the model group, positive reactions of pathological ankle joint section, inflammation, and osteoclasia degree also significantly decreased in the BSH group and the TG group (all P < 0.01). RANKL and M-CSF were significantly down-regulated in each medicated group, while levels of OPG and OPG/RANKL were significantly up-regulated (all P < 0.01). Compared with the TG group, M-CSF was lower, but levels of OPG and OPG/RANKL were significantly up-regulated in the normal control group (all P < 0.01). RANKL and M-CSF were significantly up-regulated, while levels of OPG and OPG/RANKL were significantly down-regulated in the model group and each BS group (all P < 0.01).</p><p><b>CONCLUSION</b>BTC could relieve bone damage of CIA rats possibly through regulating and controlling osteoclasts.</p>