Analysis of the Pathogenesis and Treatment of Pulmonary Nodules based on the “Six Constraints” Theory / 中医杂志

Based on ZHU Zhenheng's “six constraints” theory， it is proposed that the formation of pulmonary nodules is closely related to the six constraints， which are constraint of qi， blood， phlegm， fire， dampness and food. All six constraints might lead to pulmonary nodules， among which qi constraint is the dominant one. When qi constraint lasts for a long time， it will turn into fire constraint， resulting in the failure of spleen to transport， which may lead to phlegm constraint， dampness constraint and food constraint； when qi fails to move blood， blood constraint is formulated. Mutual generation of six constraints lead to the disease， and the pathogenesis is interrelated， jointly promoting the occurrence and development of pulmonary nodules. The treatment is mainly to unblock qi， usually using Yueju Pills （越鞠丸）， a classic formula commonly used for six constraints， as the basic formula. And according to the six constraints partiality， it is suggested to flexibly add the medicinals of soothing the liver and rectifying qi， clearing heat and dissipating masses， dissolving phlegm and dissipating masses， fortifying spleen and dissipating dampness， promoting digestion and removing accumulation， invigorating blood and dissolving stasis.

Multivariable analysis of tooth loss in subjects with severe periodontitis over 4-year natural progression / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss.@*METHODS@#A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed.@*RESULTS@#In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss.@*CONCLUSION@#In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.

Efficacy of traditional Chinese medicine combined with anti-vascular endothelial growth factor in the treatment of wet age-related macular degeneration: A systematic review and network Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical efficacy of traditional Chinese medicine(TCM)combined with intravitreal injection of anti-vascular endothelial growth factor(VEGF)or anti-VEGF medicines alone in the treatment of wet age-related macular degeneration(wAMD).METHODS:A total of eight databases were searched for relevant literatures in English and Chinese, including Chinese National Knowledge Infrastructure(CNKI), Wanfang, CQVIP, SinoMed, PubMed, Web of Science, Cochrane Library, Embase. Taking patients with wAMD as research objects, the Chinese and English clinical randomized controlled trials(RCTs)published from the databases' inception to April 20, 2022, which compared TCM combined with anti-VEGF drugs with anti-VEGF drugs alone were selected. The outcome indicators were best corrected visual acuity(BCVA)and central macular thickness(CMT). Traditional Meta and network Meta analysis were used to examine the data.RESULTS:There were 39 eligible studies among the 617 retrieved articles, involving 28 oral administration of Chinese herbal medicines and 2 757 participants. For BCVA improvement, results of TCM combination therapy were more favorable than anti-VEGF alone(MD=0.07, 95%CI: 0.05～0.09). Sheng Puhuang Decoction(SPD)ranked highest in 1 and 2mo after treatment, and Xuefu Zhuyu Capsule(XZC)ranked highest in 3mo after treatment. In terms of reducing CMT, TCM combination therapy were better(MD=-25.32 μm, 95%CI: -30.06～-20.57). Danggui Mingmu Decoction(DMD)ranked the highest in 1mo after treatment. Bushen Huoxue Decoction(BHD)ranked the highest in 2mo. Erchen Erhuang Decoction(EED)ranked the highest in 3mo.CONCLUSIONS: Compared with anti-VEGF treatment alone, TCM combination therapy led to improved BCVA and reduced CMT. However, most of the included literature is small-sample, single-center, single-blind RCTs with an overall low quality.

Loss of ATM activity induces GADD45α-dependent apoptosis in cerebellar granular neurons / 中山大学学报(医学科学版)

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Influential factors of neonatal hypoxic ischemic encephalopathy and the therapeutic effects of mild hypothermia at different time windows / 中国基层医药

Objective:To investigate the influential factors of neonatal hypoxic ischemic encephalopathy (HIE), and compare the therapeutic effects of mild hypothermia at different time windows and between different degrees of disease severity.Methods:Eighty-two neonates with HIE who were admitted to Jiaxing Maternity and Child Health Care Hospital from January 2016 to October 2021 were included in the patient group, and 123 concurrent healthy neonates were included in the control group. The influential factors of neonatal HIE were analyzed. Sixty-five neonates who received HIE were divided into four groups according to the time length between symptom onset and hospital admission (< 6 hours and 6-12 hours) and disease severity: group I (admission time < 6 hours, mild, n = 20), group II (admission time < 6 hours, moderate to severe, n = 15), group III (admission time 6-12 hours, mild, n = 17), and group IV (admission time 6-12 hours, moderate to severe, n = 13). Amplitude-integrated electroencephalography (aGGE) score was used as the evaluation criteria. The therapeutic effects of mild hypothermia were compared between different time windows and between different degrees of HIE. Results:Multivariable logistic regression analysis results revealed that the influential factors of neonatal HIE included gestational hypertension, gestational diabetes, pregnancy examination, delivery methods, amniotic fluid contamination, abnormal fetal membranes (placenta or umbilical cord), fetal distress, and neonatal asphyxia ( P < 0.05). All 65 neonates with HIE underwent mild hypothermia treatment for 72 hours. Before treatment, aGGE score in groups I, II, III and IV was 6.02 ± 1.74 points, 2.43 ± 1.82 points, 5.23 ± 1.95 points, and 2.72 ± 1.76 points, respectively. After treatment, it was 8.13 ± 2.03 points, 6.47 ± 1.87 points, 7.86 ± 1.92 points, and 3.52 ± 1.95 points, respectively. There was significant difference in aGGE score between before and after treatment in groups I, II and III ( t = 2.87, 3.55, 3.15, all P < 0.05). aGGE score in group IV did not differ significantly between before and after treatment ( P > 0.05). Before treatment, aGGE score in children with moderate to severe HIE was lower than that in children with mild HIE. After treatment, there was no significant difference in aGGE score between groups II and III ( P > 0.05). Conclusion:Pregnant women with gestational hypertension and gestational diabetes should be given intensive monitoring and learn HIE related knowledge to increase the frequency of prenatal examinations. If amniotic fluid contamination, abnormal fetal membranes (placenta or umbilical cord), fetal distress, or neonatal asphyxia occurs, timely monitoring and corresponding interventions should be given to the fetus. Mild hypothermia therapy has a certain therapeutic effect on different degrees of HIE. For moderate to severe neonates, treatment should be started within 6 hours to ensure the therapeutic effects of mild hypothermia.

Degradable high purity magnesium screw in fixing the greater trochanter bone flap pedicled with transverse branch of lateral circumflex femoral artery: Treatment of avascular necrosis of femoral head in 12 young and middle-aged patients / 中华显微外科杂志

Objective:To investigate the effect of a degradable high-purity magnesium screw in fixing the greater trochanter bone flap of a lateral circumflex femoral artery transverse branch in the treatment of ischemic necrosis of femoral head in young and middle-aged adults.Methods:From February 2017 to February 2019, 12 cases (15 hips) of young and middle-aged patients with avascular necrosis of femoral head were treated in the Department of Orthopaedic of Affiliated Zhongshan Hospital of Dalian University. The age of patients was 30-53 years old. According to Association Research Circulation Osseous (ARCO), 2 hips were graded in stage II b, 4 in ARCO II c, 1 in ARCO III a, 5 in ARCO III b, 2 in ARCO III c and 1 in ARCO IV. The greater trochanter bone flap with a lateral circumferential vascular branch was used to fill the necrotic area, and fixed by a biodegradable high purity magnesium screw in the bone flap transfer. At 3, 6 and 12 months postoperation, the patient came to the hospital outpatient clinic for follow-up, and then were reviewed once a year. Imaging efficacy was evaluated by comparing preoperative and postoperative imaging. The Harris score and Visual Anoalogue Scale (VAS) score were tested at 12 and 24 months after surgery. The Harris score and VAS score before and after surgery were compared by Friedman test, and P<0.05 was considered statistically significant. Results:All 12 patients (15 hips) were entered in the 24-36 months of follow-up. At 12 and 24 months after surgery, Harris score was found at 87 (86, 92) and 90 (87, 92) respertively, which were both higher than that before surgery [59 (52, 74)] with a significant statistical difference ( Z=-3.743, Z=-4.473, P<0.05). However, there was no significant difference in Harris scores between 12 and 24 months after the surgery ( Z=-0.730, P>0.05). At the 12 and 24 months after surgery, VAS score was found at 3 (2, 3) and 2 (1, 3) respertively, which were both lower than that before surgery [6 (5, 6) ] with a significant statistical difference ( Z=-3.560, Z=-4.656, P<0.05). There was no statistical difference in VAS scores between 12 and 24 months after surgery ( Z=-1.095, P>0.05). X-ray and CT scan showed that the bone flaps healed well and the areas of osteonecrosis were repaired. Thirteen femoral heads were in good shape, and 2 femoral heads had further collapse of hips. No patients underwent joint replacement surgery at the time of last follow-up. Conclusion:Fixation of the greater trochanter flap of lateral circumflex femoral artery transverse branch with a degradable high-purity magnesium screw can ensure the healing of the flap at the implantation site and avoid the displacement and shedding of the flap. It is a new therapeutic option to treat the avascular necrosis of femoral head of young and middle-aged people.

Research progress in the application of glass transition phenomenon in pharmaceutics / 药学学报

In recent years, the phenomenon of glass transition has been gradually applied to the field of pharmaceutics. And it exhibits important influences on multiple operating units of pharmaceutical preparations, and the properties and storage of pharmaceutical intermediates and products. At present, it has been widely used in the process of preparations such as drying, granulation, coating, tableting, holt-melt extrusion, cryogenic comminution, and so on. Meanwhile, it showed guiding significance for the process of preparation intermediates and their products, such as solid dispersion, microcapsule, liposome, particle, tablet, and other preparation intermediates and their products. Therefore, this article conducts a detailed analysis and systematic summary of the application guidance of the phenomenon of glass transition in the preparation process, and its influence on the preparation intermediates and products, so as to provide theoretical guidance for preparation production and product storage.

Application progress of acupoint sticking therapy in the treatment of malignant tumor / 国际中医中药杂志

Acupoint sticking therapy is a comprehensive Traditional Chinese Medicine treatment method combining meridian, acupoint and Chinese herbal medicine. It is widely used in the treatment of chemotherapy-related gastrointestinal reaction, cancer pain, tumor related intestinal obstruction, cancer-related fatigue, etc. It is oftenuse in conventional treatment and nursingprocess, or usedalone, or combined with oraladministration of Chinese and Western Medicine and acupoint massage. This therapy could avoid the gastrointestinal irritation caused by oral administration. The advantages are as follow: the operationis simple with obvious effect, and low price andtheacceptance is high.

Epigenetics and drug resistance in lung cancer / 国际肿瘤学杂志

Lung cancer has the highest mortality rate among malignant tumors, and drug resistance in lung cancer treatment is currently a major challenge for clinical practitioners. Recent studies have found that epigenetics is closely linked to drug resistance in lung cancer, especially in DNA methylation, histone modifications and non-coding RNA regulation. By exploring the mechanisms affecting drug resistance in lung cancer through the above three features and exploring drugs that can effectively improve drug resistance in lung cancer in response to the mechanisms, it can provide ideas for solving the problems related to drug resistance in lung cancer in clinical work and provide a reference basis for prognostic assessment of lung cancer patients.

Effect of Modified Chaihu Shugansan on Gallbladder Function and Inflammatory Cytokines Levels in Treatment of Chronic Cholecystitis Cholelithiasis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and influence of modified Chaihu Shugansan combined with ursodeoxycholic acid tablets on inflammatory factors in treatment of chronic cholecystitis cholelithiasis （stagnation of liver and gallbladder Qi）. Method:One hundred and ten patients were randomly divided into control group （60 cases） and observation group （60 cases）. Both groups received lifestyle intervention， and oral ursodeoxycholic acid tablets， 50 mg/time， taken in the morning and evening meals. Patients in control group additionally took Yidanshu capsules orally， 4 capsules/time， 3 times/day. Patients in observation group additionally took modified Chaihu Shugansan orally， 1 dose/day. The treatment courses continued 3 months in both groups. Before and after treatment， traditional Chinese medicine （TCM） symptom scores were graded， the ultrasound status of chronic gallbladder inflammation， gallbladder contraction function and stones was graded， the levels of interleukin-6 （IL-6）， IL-8， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and nuclear transcription factor-<italic>κ</italic>B（NF-<italic>κ</italic>B）Were detected， and safety was evaluated. The efficacy for TCM syndromes， imaging efficacy and the efficacy for eliminating gallbladder stones were compared between the two groups. Result:The efficacy for TCM syndrome， efficacy on color ultrasound for chronic cholecystitis and the efficacy on imaging for cholelithiasis in the observation group were all better than those in the control group（<italic>Z</italic>=2.104<italic>，Z</italic>=2.076，<italic>Z</italic>=2.101，<italic>P</italic><0.05）. The thickness of gallbladder wall and volume of the gallbladder of the observation group were smaller than those of the control group （<italic>P</italic><0.01）， and gallbladder contraction function was higher than that in control group （<italic>P</italic><0.01）. Levels of IL-6， IL-8， TNF-<italic>α</italic> and NF-<italic>κ</italic>B in observation group were lower than those in control group （<italic>P</italic><0.01）. Conclusion:modified Chaihu Shugansan combined with ursodeoxycholic acid in the treatment of chronic cholecystitis and cholelithiasis （liver and gall Qi stagnation） is better than Yidanshu capsule combined with ursodeoxycholic acid sour scheme in terms of clinical efficacy， imaging efficacy， and elimination of gallbladder stones. It can reduce inflammation， and enhance gallbladder contraction， with high safety in clinical use.

Relationship between enhancer of zeste homolog 2 mRNA level and prognosis of gastric cancer patients / 肿瘤研究与临床

Objective:To analyze the correlation between enhancer of zeste homolog 2 (EZH2) mRNA expression level and prognosis of patients with gastric cancer.Methods:The differences of the EZH2 mRNA levels between gastric cancer tissues and adjacent normal tissues and among patients with different clinical stages were analyzed by The Cancer Genome Atlas (TCGA) database. According to the median expression level of EZH2 mRNA (5.59), 368 patients were divided into high expression group (184 cases) and low expression group (184 cases). Kaplan-Meier method was used to analyze the relationship between EZH2 mRNA expression level and overall survival (OS) of patients. Multivariate Cox regression model was used to analyze the relationship between age, clinical stage, TNM stage, gender, EZH2 mRNA expression level and OS. The relationships between EZH2 mRNA expression level and OS in all gastric cancer patients, human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative patients were analyzed by KM-plotter online database. The KEGG pathway enrichment analysis of tumor samples from TCGA-STAD collection in the TCGA database was carried out by using GSEA software, and enrichment score (ES), normalized enrichment score (NES), nominal P value (NOM p-val) and multiple testing correction (FDR q-val) were calculated. KEGG pathways related to tumorigenesis were screened according to FDR q-val < 0.25. Results:Among 375 cases of gastric cancer tissues in the TCGA database, the level of EZH2 mRNA in 171 cases were low and the level of EZH2 mRNA in 204 cases were high; the level of EZH2 mRNA in 32 cases of adjacent normal tissues were low. The median EZH2 mRNA expression level in adjacent normal tissues was 1.73, and the median EZH2 mRNA expression level in tumor tissues was 5.59. The expression level of EZH2 mRNA in gastric cancer tissues was higher than that in normal adjacent tissues, and the difference was statistically significant ( u = 925, P < 0.05). There was no significant difference in EZH2 mRNA expression level between patients with different clinical stages ( DF = 3, P = 0.25). Kaplan-Meier analysis showed that patients with high expression of EZH2 mRNA had longer OS time than those with low expression of EZH2 mRNA ( HR = 0.623, P = 0.008). Univariate Cox analysis showed that EZH2 mRNA level was one of the independent risk factors for OS in patients ( HR = 0.666, P = 0.024). In the KM-plotter database, patients with high expression of EZH2 mRNA (632 cases) had longer OS time than patients with low expression of EZH2 mRNA (244 cases) ( HR = 0.75, P = 0.002). In patients with positive HER2 (344 cases), patients with high expression of EZH2 mRNA had a shorter OS time ( HR = 1.31, P = 0.042), while in patients with negative HER2 (532 cases), patients with low expression of EZH2 mRNA had a shorter OS time ( HR = 0.57, P < 0.05). GSEA enrichment found that EZH2 mRNA was related to a variety of tumor-related pathways and cell synthesis and metabolism pathways. Conclusion:The expression of EZH2 mRNA is related to the prognosis of patients with gastric cancer, and it may be used as a biomarker for evaluating the prognosis of patients with gastric cancer.

Mechnism research progress of the intervention of traditional Chinese medicine compound on gastric cancer / 国际中医中药杂志

This article reviewed the research on the intervention of traditional Chinese medicine compound on gastric cancer. And to discover the traditional Chinese medicine with anti-tumor effect and traditional Chinese medicine ingredients have an effect on the development of tumor, such as influencing the precancerous lesions, inhibiting tumor cell proliferation, metastasis, by inhibiting tumor blood vessels to grow. It will influence tumor cell apoptosis pathway and inflammatory response. TCM compound intervention can improve human immunity, so as to prevent and treat gastric cancer.

Mechnism research progress of the intervention of traditional Chinese medicine compound on gastric cancer / 国际中医中药杂志

This article reviewed the research on the intervention of traditional Chinese medicine compound on gastric cancer. And to discover the traditional Chinese medicine with anti-tumor effect and traditional Chinese medicine ingredients have an effect on the development of tumor, such as influencing the precancerous lesions, inhibiting tumor cell proliferation, metastasis, by inhibiting tumor blood vessels to grow. It will influence tumor cell apoptosis pathway and inflammatory response. TCM compound intervention can improve human immunity, so as to prevent and treat gastric cancer.

Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain / 神经科学通报·英文版

The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on depression-like behaviors in mice and to explore the potential mechanisms. These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naïve and space-restriction-stressed (SRS) mice, reflected by a decreased duration of immobility in behavioral despair tests. BoNT/A significantly increased the 5-hydroxytryptamine (5-HT) levels in several brain regions, including the hippocampus and hypothalamus, in SRS mice. BoNT/A increased the expression of the N-methyl-D-aspartate receptor subunits NR1 and NR2B in the hippocampus, which were significantly decreased in SRS mice. Furthermore, BoNT/A significantly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which were decreased in SRS mice. Finally, BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP-response element binding protein (p-CREB), which were suppressed in the hippocampus of SRS mice. Collectively, these results demonstrated that BoNT/A treatment has anti-depressant-like activity in mice, and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus, supporting further investigation of BoNT/A therapy in depression.

Correction to: Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain / 神经科学通报·英文版

In the original publication, Figure 4G was incorrectly published. The correct version of Figure 4G is presented in this correction. This correction does not affect the conclusions of the paper.

Effect of long non-coding RNA F19 on secondary brain injury after traumatic brain injury in mice / 中华创伤杂志

Objective To investigate the effect of long non-coding RNA F19 (lncRNA F19) on secondary brain injury following traumatic brain injury (TBI) in mice. Methods (1) A total of 96 C57BL/6J male wild-type mice were divided into sham group, sham+control lentivirus group, sham+F19 lentivirus group, TBI group, TBI+control lentivirus group and TBI+F19 lentivirus group according to the random number table. Each group consisted of two subgroups of 1 day and 3 days after TBI, with eight mice per subgroup. The expression and silence efficiency of lncRNA F19 were detected. ( 2 ) A total of 96 C57BL/6J male wild-type mice were divided into sham group, TBI+control lentivirus group and TBI + F19 lentivirus group according to the random number table. Each group consisted of two subgroups of 1 day and 3 days after TBI, with 16 mice per subgroup. The effect of lncRNA F19 on neuronal apoptosis after TBI was recorded. The mice TBI model was established using the controlled cortical damage method (CCI). The lncRNA F19 lentivirus or control lentivirus were administrated by intracerebroventricular injection 5 days before injury. The expressions of lncRNA F19 ( 2 -ΔΔct ) were detected by real-time quantitative PCR ( qRT-PCR ) at 1 day and 3 days after injury. The Toll-like receptor 4 (TLR4), B lymphocyte tumor-2 (Bcl-2) and Bcl-2 related protein (Bax) expressions were detected by Western blot. The TUNEL was used to detect apoptosis around the traumatic lesions. Results From the first day after injury, both in the sham operation and TBI groups, the control lentivirus had no effect on the level of lncRAN F19 (P >0. 05). One day after injury, compared with sham +control lentivirus group, the levels of lncRNA F19 in sham + F19 lentivirus group were significantly decreased (0. 07 ± 0. 07:0. 93 ± 0. 17);compared with TBI+control lentivirus group, levels of lncRNA F19 in TBI+F19 lentivirus group were significantly decreased (2. 91 ± 1. 18:0. 52 ± 0. 32) (P<0. 05). There were significantly lower protein levels of TLR4 (0. 51 ± 0. 13:0. 66 ± 0. 15), Bax (0. 45 ± 0. 06:0. 67 ± 0. 16), lower TUNEL-positive neurons ratio [(23. 55 ± 6. 85)％ : (31. 58 ± 7. 52)％], but higher protein levels of Bcl-2 (0. 76 ± 0. 16:0. 47 ± 0. 12) in TBI+F19 lentivirus group compared with the TBI+ control lentivirus group (P <0.05). Three days after injury, compared with sham + control lentivirus group, levels of lncRNA F19 in sham+F19 lentivirus group were significantly decreased (0. 11 ± 0. 09:0. 96 ± 0. 09); compared with TBI+control lentivirus group, levels of lncRNA F19 in TBI+F19 lentivirus group were significantly decreased (0. 54 ± 0. 24:3. 39 ± 0. 90) (P <0. 05). There were significantly lower protein levels of TLR4 (0. 60 ± 0. 20):(0. 85 ± 0. 09)], lower Bax (0. 60 ± 0. 12:0. 88 ±0. 21), lower TUNEL-positive neurons ratio [(29. 10 ± 7. 37)％ :(39. 22 ± 10. 64)％], but higher protein levels of Bcl-2 (0. 66 ± 0. 12:0. 35 ± 0. 16) in TBI+F19 lentivirus group compared with the TBI+control lentivirus group (P<0. 05). Conclusion Inhibition of lncRNA F19 can significantly reduce the TLR4-induced neuronal apoptosis in cortex after TBI in mice and alleviate reduce the secondary brain injury.

Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: Five members of the zinc finger of the cerebellum (ZIC) family—ZIC1, ZIC2, ZIC3, ZIC4, and ZIC5—have been shown to be involved in various carcinomas. Here, we aimed to explore the clinicopathologic and prognostic roles of ZIC family members in invasive breast cancer patients using immunohistochemical analysis, western blotting analysis, and real-time quantitative polymerase chain reaction (RT-qPCR). METHODS: A total of 241 female invasive breast cancer patients who underwent radical mastectomy between 2009 and 2011 were enrolled. ZIC proteins in 241 pairs of breast tumors and corresponding normal tissues were investigated using immunohistochemistry and the clinicopathologic roles of proteins were analyzed using Pearson's chi-square test. Kaplan-Meier curves and Cox regression analysis were also used to analyze the prognostic value of the ZIC proteins. In addition, 12 pairs of fresh-frozen breast tumors and matched normal tissues were used in the western blotting analysis and RT-qPCR. RESULTS: Only ZIC1 expression in normal tissues was obviously higher than that in tumors (p < 0.001). On multivariate analysis, ZIC1 expression (in overall survival analysis: hazard ratio [HR], 0.405, 95% confidence interval [CI], 0.233–0.702, p=0.001; in disease-free survival analysis: HR, 0.395, 95% CI, 0.234–0.669, p=0.001) was identified as a prognostic indicator of invasive breast cancer. CONCLUSION: ZIC1, but not the other proteins, was obviously decreased in breast tumors and associated with clinicopathologic factors. Thus, ZIC1 might be a novel indicator to predict the overall and disease-free survival of invasive breast cancer patients.

A Highly Sensitive Fluorescent Probe for Detection of Magnesium Ion(Ⅱ) Based on Novel Schiff's Base / 分析化学

A highly sensitive fluorescent probe TZ based on a novel Schiff's base was prepared for detection of Mg2+. It was constituted by introducing dansyl chloride and 2-hydroxy-1-naphthaldehyde through amino and hydrazide groups on p-aminobenzoyl hydrazide. The recognition mechanism of the fluorescent probe TZ for Mg2+was studied by electrospray ionization mass spectrometry (ESI-MS), UV-vis and fluorescence spectra. UV-vis spectra showed that the probe TZ had a characteristic absorption peak of naphthalene aldehyde at 386. 5 nm,and a new absorption peak at 411 nm was observed after coordination between TZ with Mg2+. A sharp isobestic point was obtained at 400 nm. Fluorescence spectra showed that the emission wavelength was red-shifted to 400 nm upon the addition of Mg2+into probe TZ. The fluorescence intensity was enhanced by 10 times at the emission wavelength of 468 nm and the quantum yield of 0.57 was obtained. Moreover,chemical bond energy transfer was found when 2-hydroxy-1-naphthaldehyde was coordinated with Mg2+. When the other metal ions (Li+,Na+,K+,Zn2+,Ca2+, Mn2+, Cd2+, Pb2+, Ag+, etc.) were added into TZ, no significant change of fluorescence intensity was observed. It indicated that TZ had high selectivity to Mg2+. Furthermore, the recognition of TZ to Mg2+was not interfered by other competing metal ions. ESI-MS titration and Job's plot analysis confirmed that 1: 1 complexation stoichiometry between TZ and Mg2+was obtained. The lowest detection limit was up to 0.13 μmol/L.

Human amnion epithelial cell transplantation provides a local repair of liver damage induced by carbon tetrachloride in mice / 中国组织工程研究

BACKGROUND: Human amnion epithelial cells (hAECs) have many merits that embryonic stem cells and adult stem cells do not have, such as no tumorigenicity, rich sources, easy to obtain, low immunogenicity and no medical ethics limit. Therefore, hAECs are expected to be important seed cells for clinical transplantation. OBJECTIVE: To observe the therapeutic effect of hAECs transplantation labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) in a mouse model of liver damage induced by carbon tetrachloride. METHODS: hAECs from the human amniotic membrane were collected using enzymatic digestion, and morphology of cells was observed. Expression of keratin 19 in hAECs was detected by immunocytochemistry. Model of liver damage was made in mice by intraperitoneal injection of carbon tetrachloride.Then,CFSE-labeled hAECs were injected into the liver damage mice via tail vein.Histopathological changes and liver function in mice were observed at 7 and 30 days after transplantation, respectively. RESULTS AND CONCLUSION: The high-purity hAECs were successfully isolated, which expressed keratin 19 shown by immunocytochemical staining. Frozen sections of immunoflrorescence showed that hAECs could be moved to the damaged liver, and exhibited remarkable repair effects on the liver function and histopathology in mice. These findings indicate that hAECs can be used for xenotransplantation and function to promote physiological recovery from liver injury, thereby providing experimental evidence for liver repair with cell transplantation.