A case of duodenal ulcer as prominent manifestation of IgG4-related disease / 北京大学学报(医学版)

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms / 神经科学通报·英文版

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.

Analysis of success rate of organoid construction of nasopharyngeal carcinoma by first-day suspension method / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.

Changes of uterine morphology and endometrial T2 signal intensity in the fibrotic repair secondary to endometrial injury / 中华妇产科杂志

Objective: To investigate the value of uterine morphological parameters and endometrial T2 signal intensity (T2-SI) in evaluating the degree of the fibrotic repair secondary to endometrial injury. Methods: From Sep. 2018 to Feb. 2023, this study prospectively enrolled 29 patients with fibrotic repair secondary to severe endometrial injury (severe group), 17 patients with fibrotic repair secondary to mild to moderate endometrial injury (mild to moderate group), and 40 healthy women of reproductive age (control group) in Nanjing Drum Tower Hospital. The length of uterine cavity (LUC), length of cervix and isthmus (LCI), width of upper uterine cavity (WUUC) and width of lower uterine cavity (WLUC) were measured using magnetic resonance imaging. T2-SI of endometrium and subcutaneous fat of buttocks were measured, and endometrial normalized T2-SI (nT2-SI; T2-SI of endometrium/T2-SI of subcutaneous fat of buttocks) was calculated. Statistical analyses of data were performed using one-way analysis of variance, Mann-Whitney U test, intraclass correlation coefficient, Spearman rho test, area under the receiver operating characteristic curve (AUC). Results: LUC, WUUC, WLUC and endometrial nT2-SI of severe group [(19.7±3.5) mm, (26.9±6.4) mm, (7.9±1.4) mm, 0.73±0.11, respectively] were significantly lower than those of the control group (all P<0.01), while LCI and WUUC/LUC [(51.3±7.3) mm and 1.38±0.34] were significantly higher than those of the control group (all P<0.001). LUC and WLUC of severe group were significantly lower than those of mild to moderate group [(32.4±5.1) mm and (8.8±1.2) mm; all P<0.05], while LCI and WUUC/LUC were significantly higher than those of mild to moderate group [(41.8±8.6) mm and 0.94±0.16; all P<0.001]. LUC and endometrial nT2-SI of mild to moderate group were significantly lower than those of the control group [ (32.4±5.1) vs (35.3±3.5) mm, 0.68±0.13 vs 0.80±0.12; all P<0.01]. LUC, WUUC, WLUC and endometrial nT2-SI were significantly negatively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho:-0.794, -0.441, -0.471 and -0.316, respectively; all P<0.05), while LCI and WUUC/LUC were significantly positively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho: 0.481 and 0.674, respectively; all P<0.05). LUC and WUUC/LUC showed high value in distinguishing severe group from the control group or mild to moderate group (all AUC>0.9, all P<0.001). Conclusion: As noninvasive and quantitative biomarkers, uterine morphological parameters and endometrial nT2-SI could evaluate the degree of the fibrotic repair secondary to endometrial injury.

Protective Effects of Raspberry Crude Polysaccharides on UVB-Induced Photodamage in HaCaT Cells / 中国生物化学与分子生物学报

Polysaccharide is one of the functional components of the raspberry, which has various pharmacological effects such as anti-inflammatory, antioxidant, anti-fatigue, hypoglycemic and immunomodulatory. However, whether raspberry polysaccharides have protective effects on UV-induced photodamage to skin cells has not been reported. This study aims to investigate the protective effect of Raspberry Crude Polysaccharide on Ultraviolet B (UVB) -induced photodamage of human immortalized keratinocytes (H a C a T). The photodamage model of HaCaT cells was established by UVB irradiation. To evaluate the anti-UVB activity of R C P, the cell viability was determined by the CCK-8 method, and the Enzyme-linked immunosorbent assays (ELISA) and microplate method were used to measure the contents of matrix metalloproteinase, inflammatory and antioxidant factors in the photodamaged HaCaT cells. The antioxidant activity of RCP was detected by radical scavenging assays against D P P H radical (D P P H •) and ABTS radical (ABTS •

ACT-FAST: a quality improvement project to increase the percentage of acute stroke patients receiving intravenous thrombolysis within 60 minutes of arrival at the emergency department

INTRODUCTION@#Stroke is a leading cause of death and disability, with the administration of recombinant transcriptase-plasminogen activator (rtPA) improving outcomes in a time-dependent manner. Only 52.3% of eligible stroke patients at our institution received rtPA within 60 minutes of arrival. We aimed to improve the percentage of acute stroke patients receiving rtPA within 60 minutes of arrival at the emergency department (ED).@*METHODS@#This study presents results from the first year of a clinical practice improvement project that implemented quality improvement interventions. The primary outcome measure was percentage of acute ischaemic stroke patients receiving rtPA within 60 minutes of arrival at the ED. Secondary outcome measures included components of total door-to-needle (DTN) time and factors for delay to thrombolysis. Interventions were establishment of standardised acute stroke activation guidelines, screening question at ED registration, prehospital notification of stroke activation, public education, scripting for thrombolysis consent and easy access to equipment.@*RESULTS@#The percentage of patients thrombolysed within 60 minutes increased to 60.6% (p = 0.27), and DTN time decreased from 59 minutes to 54.5 minutes (p = 0.15). This was attributable to reduced door-to-physician time, door-to-imaging time and decision time, although the results were not significant. There was no significant increase in symptomatic intracranial haemorrhage or mortality secondary to stroke. Length of stay was significantly reduced by 1.5 days (p < 0.048).@*CONCLUSION@#The interventions resulted in an increasing but non-significant trend of acute stroke patients receiving thrombolysis within 60 minutes. Outcomes will be monitored for a longer duration to demonstrate trends and sustainability.

CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice / 神经科学通报·英文版

Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3

TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice / 神经科学通报·英文版

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca

CCL2/CCR2 Contributes to the Altered Excitatory-inhibitory Synaptic Balance in the Nucleus Accumbens Shell Following Peripheral Nerve Injury-induced Neuropathic Pain / 神经科学通报·英文版

The medium spiny neurons (MSNs) in the nucleus accumbens (NAc) integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output. Here we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation (SNL). SNL increased the frequency, but not the amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs), and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the MSNs. SNL also decreased the paired-pulse ratio (PPR) of evoked IPSCs but increased the PPR of evoked EPSCs. Moreover, acute bath application of C–C motif chemokine ligand 2 (CCL2) increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs, and especially strengthened the amplitude of N-methyl-D-aspartate receptor (NMDAR)-mediated miniature EPSCs. Further Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ratio. Finally, Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression (LTD) in the NAc after SNL. These results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.

A case report of colchicine-induced myopathy in a patient with chronic kidney disease / 北京大学学报(医学版)

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.

Bioinformatics Analysis and Verification of Acute B-Lymphocytic Leukemia in Children with Isolated Bone Marrow Relapse / 中国实验血液学杂志

OBJECTIVE@#To analyze the hub genes affecting the solely bone marrow relapse of childish acute B-cell lymphoblastic leukemia (B-ALL).@*METHODS@#The high-throughput RNA sequencing data were downloaded from TCGA database, the differentially expressed genes were screened by DESeq2 package of R, and the differentially expressed genes were grouped by GO function enrichment analysis and KEGG pathway enrichment analysis. Further, the data of STRING database and Cytoscape software were used to construct protein interaction network, screen hub genes and highly interaction protein sub network, perform GO and KEGG analysis of the hub genes and protein sub network respectively. JASPAR database was used to screen the upstream transcription factor of the hub gene promoter. Survival analysis based on the expression of hub genes was performed with clinical information attached to TCGA database. The bone marrow samples and clinical data of the patients were collected, the analysis results of hub genes were verified through clinical samples.@*RESULTS@#847 differentially expressed genes were collected, including 813 up-regulated genes, 34 down-regulated genes, 11 hub genes were screened out. The results of survival analysis showed that RPS5、RPS15、RPL23、RPL35、RPS8、RPS27A、RPS3、RPL9、RPS21、RPS7 and RPL38 showed significant effect on the survival of the children, and ZNF460 might be involved in their regulation. The high expressions of RPS3, RPS15, RPS8, RPS27A, and RPS21 had been verified in clinical samples of solely bone marrow relapsed patients.@*CONCLUSION@#RPS3, RPS15, RPS8, RPS27A, RPS21 can be used as biomarkers to indicate the malignant event of solely bone marrow relapse, which may be regulated by ZNF460.

Grading of Seed Rhizoma for Curcuma phaeocaulis and Its Effect on Plant Growth， Yield and Quality of Medicinal Materials / 中国实验方剂学杂志

Objective:To establish the grading standard of <italic>Curcuma phaeocaulis</italic> seed rhizoma，and explore the effect of seed rhizoma classification on the growth，yield and quality of <italic>C. phaeocaulis</italic>. Method:The purity，diameter，weight，length，germination rate and water content of <italic>C. phaeocaulis</italic> seed rhizoma samples were determined. The grading index was determined by partial correlation analysis，variance analysis and cluster analysis. According to actual conditions of production，the classification standard of<italic> C. phaeocaulis</italic> seed rhizoma was established. Then the field experiments were carried out with different grades of seed rhizoma for treatment， so as to analyze the effect of seed rhizoma grade on plant growth，yield and quality of medicinal materials. Result:With seed rhizoma diameter and seed rhizoma weight as classification indexes，<italic>C. phaeocaulis</italic> seed rhizoma were divided into three grades. The field experiments showed that with the growth and development of <italic>C. phaeocaulis</italic>，there were significant differences in plant height and leaf length among different grades of seed rhizoma during the root tuber expansion period （<italic>P</italic><0.05）. The yield of Curcumae Radix and Curcumae Rhizoma produced by different grades of seed rhizoma was in the order of first-class ginger>second-class ginger>third-class ginger>substandard seed rhizoma. According to the analysis of the proportion of the commodity grade of medicinal materials，the higher the grade of seed rhizoma was，the higher the proportion of the first-grade Curcumae Radix occupied. According to the analysis of the quality of medicinal materials，there was no significant difference in the content of extract，volatile oil and germanone in Curcumae Radix and Curcumae Rhizoma produced by different grades of seed rhizoma. Conclusion:The grading standard of seed rhizoma was established based on the systematic study on the classification method of <italic>C. phaeocaulis</italic> seed rhizoma. According to the field experiment， grading planting of seed rhizoma can promote plant growth and development，increase the yield of medicinal materials，and improve the proportion of first-grade medicinal materials， with no impact on the internal quality of medicinal materials. Therefore， classification of <italic>C. phaeocaulis</italic> seed rhizoma is scientific and necessary，and can lay the foundation for the standardized cultivation of <italic>C. phaeocaulis</italic>.

Comparative Study on the Quality Differences of Pinelliae Rhizoma with Different Diameter / 中国药房

ABSTRACT OBJECTIVE：To investigate the quality differences of Pinelliae Rhizoma with different diameter，and to providereference for the rational utilization of its resources. METHODS：A total of 65 batches of commercial Pinelliae Rhizoma from thefour major medicinal markets in China and two companies were collected as samples，the diameter of them were measured byvernier caliper，and then them were screened into samples with different diameter ranges（0.5 cm≤d≤0.8 cm，0.8 cm＜d≤1.0cm，1.0 cm＜d≤1.2 cm，1.2 cm＜d≤1.5 cm，1.5 cm＜d≤2.0 cm）by sieving. The content of organic acids（oxalic acid，citricacid，L-malic acid，succinic acid，fumaric acid，trans-aconitic acid and cis-aconitic acid）in Pinelliae Rhizoma samples of differentdiameter ranges were determined by HPLC，and the content of the extracts of Pinelliae Rhizoma samples of different diameterranges were determined by cold leaching method according to 2201 general principles in 2015 edition of Chinese Pharmacopoeia（Part Ⅳ），to evaluate the quality difference of Pinelliae Rhizoma in different diameter ranges.73 batches of Pinelliae Rhizoma fromcorresponding 10 main producing areas were collected as samples，to investigate its distribution of diameter. RESULTS：Dtermination of 65 batches of commercial Pinelliae Rhizoma showed that the content of organic acids and extracts in PinelliaeRhizoma increased with the increase of its diameter in general. However，there were no significant difference in organic acids andcontent of the extracts among Pinelliae Rhizoma samples of different diameter ranges in the same batch（P＞0.05）. The diameter distribution of 73 batches of Pinelliae Rhizoma from corresponding areas was mainly between 0.6 cm and 1.8 cm，with an averageweight of 95.54％. If the diameter standard（1-1.5 cm）specified in the 2015 edition of Chinese Pharmacopoeia（part Ⅰ）wasadopted，only 8 of 73 batches of Pinelliae Rhizoma meet the requirements，and the qualified rate was 10.96％；if the diameterrange was properly expanded to 0.7-1.5 cm，54 batches of Pinelliae Rhizoma meet the requirements，with a qualified rate of73.97％；when the diameter range was expanded to 0.7-1.6 cm，68 batches of Pinelliae Rhizoma meet the requirements，with aqualified rate of 93.15％ .CONCLUSIONS：There is no significant difference in the quality of Pinelliae Rhizoma with different diameters. Combined with the diameter distribution of Pinellia Rhizoma in different producing areas，the diameter range of 1-1.5cm specified in relative standard can be expanded to 0.7-1.6 cm，avoiding the waste of resources.

E-cadherin Expression in Children with Acute Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation of E-cadherin expression level with the clinical characterastics in children with acute leukemia (AL), and to explore the possible regulatory mechanism.@*METHODS@#Real-time quantitative RT-PCR was applied to detect the expression level of E-cadherin in bone marrow samples from 135 child patients diagnosed as AL, and its relevance with clinical indicators was statistically analyzed. The expression levels of E-cadherin, β-catenin, and Akt/p-Akt were detected by using Western blot. The bone marrow samples from 22 children with non-malignant hematological diseases were used as controls.@*RESULTS@#The expression level of E-cadherin significantly decreased in newly diagnosed patients with all 3 types of AL as compared with bone marrow samples from control group (P0.05). The expression level of E-cadherin in the patients from Common-B-ALL group was higher than B-ALL patients with other immunophenotypes (P<0.01), while no significant difference was found among patients grouped by FAB classification. By the correlation analysis of measured data, lower E-cadherin expression level was found to be related with high WBC count and serum lactic dehydrogenase level (LDH) (r=-0.419, r=-0.269), but with low blood platelet count in B-ALL (r=0.335). In T-ALL, expression of E-cadherin was found to be negatively correlated with LDH and percentage of immature cells in the bone marrow (r=-0.567, r=-0.557). In addition, the lower expression of E-cadherin was also found to be related with WBC count and percentage of immature cells in the bone marrow in newly diagnosed AML patients (r=-0.368, r=-0.391). Compared with control group, the expression of E-cadherin was down-regulated significantly (P<0.01), while β-catenin, Akt significantly was up-regulated in 3 types of AL patients (P<0.01). The expression of p-Akt and p-Akt/Akt was up-regulated significantly in T-ALL (P<0.01).@*CONCLUSION@#Lower expression of E-cadherin is related factor of unfavourable prognosis in children with acute leukemia. The expression deficiency or down-regulation of E-cadherin may activate Wnt/β-catenin and PI3K/ Akt signaling pathways to promote the genesis and progress of haematological malignancies, thus resulting in a series of malignant biological behaviors in cells. E-cadherin may be a new prognostic indicator for pediatric acute leukemia, thus to guide individualized hemotherapy.

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion / 神经科学通报·英文版

Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. Our recent study indicated that C-X-C motif chemokine 13 (CXCL13) and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation (SNL). Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown. Here, we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL. Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic pain-related place avoidance behavior. Furthermore, electrophysiological recording from layer II-III neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), decreased the EPSC paired-pulse ratio, and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio, indicating enhanced glutamatergic synaptic transmission. Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

Synthesis of trifluoromethyl-substituted mono-carbonyl curcumin analogs and evaluation of their anti-proliferation activity on lung cancer cells / 国际药学研究杂志

Objective To synthesize trifluoromethyl-substituted mono-carbonyl curcumin analogs and investigate their effects on the proliferation of human lung cancer cells A549 and NCI-H460. Methods Six mono-carbonyl curcumin analogs 1a-1f were synthesized via Aldol condensation using commercially available 2-trifluoromethyl benzadehyde and different ketones (actone, cyclopentanone, cyclohexanone, piperid-4-one, and 1-methylpiperid-4-one). MTT method was used to test the effect of 1a-1f on the proliferation of A549 and NCI-H460 cells. Results Compared with curcumin, most of the mono-carbonyl curcumin analogs 1a-1f exhibited anti-proliferation activity on the A549 cells. The values of IC50 were lower than that of curcumin (P＜0.01), and 1a and 1f showed much better activities both on the A549 and NCI-H460 cells, with their IC50 values were much lower than that of curcumin (P＜0.01).Among them, 1f showed better medicinal chemical properties, with the relative molecular mass less than 500, cLogP 5.25, and the polar surface area (PSA) 37.38, which was more better accorded with the Lipinski′s five rules. Conclusion Six mono-carbonyl curcumin analogs 1a-1f were synthesized, and 1f showed much better anti-proliferation activity on A549 and NCI-H460 cells.

Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms / 神经科学通报·英文版

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2) neurons. CCL2 increased NMDA-induced currents in CCR2/VGLUT2 neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice / 神经科学通报·英文版

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

An overview of the removal of algal toxins by water treatment process / 军事医学

The environmental and health problems caused by the frequent occurrence of cyanobacteria blooming and its secondary metabolites,algal toxins, have become a hot spot in environmental science research.This article reviews the production and contamination status of algal toxins, and the removal effects of microcystins(MCs), anatoxin-a(ANTX) and other algal toxins by different water treatment processes, including coagulation and sedimentation, ozone oxidation, activated carbon adsorption,membrane treatment, chlorination and UV irradiation.Furthermore, the factors affecting the removal effect are analyzed,and the advantages and limitations of each water treatment process are summarized.Finally, some feasible proposals are presented regarding the future research of removing algal toxins.

Clinical outcome analysis on using extensor digitorum communis splitting approach for the treatment of radial head fractures / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical outcomes of internal fixation or replacement for the treatment of radial head fractures through the extensor digitorum communis splitting approach.</p><p><b>METHODS</b>From July 2012 to May 2015, 25 patients with radial head fractures were reviewed. There were 17 males and 8 females, ranging in age from 20 to 67 years old, with a mean age of 39 years old. Twenty-one patients were treated with reconstruction of plate internal fixation, and 4 patients were treated with radial head replacement. According to Mason classification, 19 cases were type II and 6 cases were type III. All the patients underwent internal fixation or replacement through the extensor digitorum communis splitting approach. The patients were followed up clinically and radiographically until the beginning of fracture union and the entrance of function recovery of elbow motion into a plateau. The functional status of the elbow was evaluated using the Mayo Elbow Performance Index(MEPI). Radiographic signs of post-traumatic arthritis were rated according to the Broberg and Morrey system.</p><p><b>RESULTS</b>All the patients were followed up, and the average duration was 29 months (ranged, 12 to 56 months). The average range of flexion and extension was 120°, the extension was limited by 10°, and the flexion was 135°. The average forearm rotation range was 142°, pronation was 75°, supination was 67°. The mean MEPI was 93±7(ranged, 80 to 100 scores); according to the MEPI scoring criceria, 19 patients got an excellent functional result, 6 good. According to the Broberg and Morrey systems of traumatic arthritis, 19 patients were in grade 0, 6 in grade 1, and no patients in grade 2 or 3. No patients with nonunion of the radial head and failure of internal fixation were found. There were no complications of nerve or vascular injuries, and obvious limitation of elbow rotation. Heterotopic ossification around the elbow occurred in 4 cases, but the motion was not significantly limited. There were no complications such as prosthesis loosening and infection in 4 cases after radial head prosthesis replacement.</p><p><b>CONCLUSIONS</b>The extensor digitorum communis splitting approach is an effective exposure method for internal fixation or replacement in the treatment of radial head fractures.</p>