Crotonoids A-H, Labdane-Type Diterpenoids with Anti-Inflammatory Activity from Croton sublyratus.

Croton sublyratus (Euphorbiaceae) is a traditional medicinal plant used by the Thai populace to treat helminthic infections and dermatologic conditions. In present study, eight new labdane-type diterpenoids, crotonoids A-H (1-8) and one known analogue (9) were isolated from the aerial parts of C. sublyratus. Compounds 6 and 7 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compound 8 exhibited a rare 14,15,17-trinor-labdane skeleton. The structures of all these diterpenoids were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound 9 exhibited moderate anti-inflammatory activity via the inhibition of NO production in lipopolysaccharide-induced RAW 264.7 cells.

Development of broad-spectrum immunoassay with monoclonal antibody to detect five eugenols and study of their molecular recognition mechanism.

In this study, three eugenol fragment-containing haptens were synthesized, and a monoclonal antibody (mAb) selective for five commonly-found eugenol compounds (EUGs, i.e., eugenol, isoeugenol, methyl eugenol, methyl isoeugenol, and acetyl isoeugenol) was obtained. Based on this mAb, a broad-spectrum indirect competitive ELISA for high-throughput detection of five EUGs was developed. The detection limits for eugenol, isoeugenol, methyl eugenol, methyl isoeugenol and acetyl isoeugenol in both tilapia and shrimp samples were 25.3/ 50.6 µg/kg, 0.075/0.15 µg/kg, 0.48/0.96 µg/kg, 0.16/0.32 µg/kg, and 18.16/36.32 µg/kg, respectively. The recoveries for five EUGs ranged from 80.4 to 114.0 % with a coefficient of variation less than 11.5 %. Moreover, homology modelling and molecular docking were conducted to elucidate the interactions mechanism of mAb-EUGs. The work provides a promising tool for high-throughput screening of EUGs in aquatic products, which can serve as a benchmark for designing haptens and developing immunoassays for other small molecules.

Elevated levels of loneliness in migrant children compared to nonmigrant children in urban China: a systematic review and meta-analysis of comparative studies.

PURPOSE OF REVIEW: About one in four children in China is a migrant child. This population has a higher risk of experiencing loneliness. However, existing studies present conflicting findings regarding the levels of loneliness among migrant children as compared to local urban children in urban China. This review performs a meta-analysis of studies comparing loneliness levels between these two groups. RECENT FINDINGS: A literature search of major Chinese- and English-language databases revealed 27 eligible comparative studies. These studies reported the means and standardized deviations of loneliness scores for both migrant and nonmigrant children in urban China. Meta-analysis results showed that migrant children experienced significantly higher levels of loneliness than their urban nonmigrant counterparts [standardized mean difference (SMD) = 0.21, P  < 0.001]. Subgroup analysis revealed that studies enrolling migrant children from migrant children's schools had significantly higher pooled SMDs than those enrolling children from public schools (0.346 vs. 0.120, P  = 0.047). SUMMARY: Migrant children in urban China experience higher levels of loneliness compared to their local urban peers. Efforts to create a socially inclusive, migrant-friendly environment and reduce social isolation among migrant children are crucial to help alleviate their feelings of loneliness.

Diffuse arterial atherosclerosis presenting with acute ischemic gastritis: A case report.

BACKGROUND: Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopathologically. Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear. CASE SUMMARY: A 68-year-old woman with a history of intracranial aneurysm developed dizziness, chest tightness and unconsciousness for 2 d. Computed tomography angiography showed diffuse coronary atherosclerosis, moderate to severe stenosis in the proximal end of the left anterior descending branch, multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery, and mild to moderate stenosis. The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries, with mild lumen stenosis and atherosclerosis in the abdominal aorta and its branches. Endoscopy showed submucosal congestion and damage of the entire gastric mucosa, of which the fundus and body of the stomach were most seriously affected. The mucosa was swollen, with a deep purple color, surface erosion and dark red oozing blood. Pathological examination showed bleeding and necrosis of the gastric mucosa, with residual contours of the gastric glands, consistent with ischemic gastritis. CONCLUSION: Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases. Diagnosis is usually based on endoscopic and pathological examinations, which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.

Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation.

Vaccinia virus (VACV) encodes scores of proteins that suppress host innate immunity and many of these target intracellular signalling pathways leading to activation of inflammation. The transcription factor NF-κB plays a critical role in the host response to infection and is targeted by many viruses, including VACV that encodes 12 NF-κB inhibitors that interfere at different stages in this signalling pathway. Here we report that VACV proteins C2 and F3 are additional inhibitors of this pathway. C2 and F3 are BTB-Kelch proteins that are expressed early during infection, are non-essential for virus replication, but affect the outcome of infection in vivo. Using reporter gene assays, RT-qPCR analyses of endogenous gene expression, and ELISA, these BTB-Kelch proteins are shown here to diminish NF-κB activation by reducing translocation of p65 into the nucleus. C2 and F3 are the 13th and 14th NF-κB inhibitors encoded by VACV. Remarkably, in every case tested, these individual proteins affect virulence in vivo and therefore have non-redundant functions. Lastly, immunisation with a VACV strain lacking C2 induced a stronger CD8+ T cell response and better protection against virus challenge.

5-Hydroxymethylcytosine profiles in plasma cell-free DNA reflect molecular characteristics of diabetic kidney disease.

Background: Diabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions. Methods: We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database. Results: This study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1). Conclusions: The 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD.

An Alternatively Spliced Variant of METTL3 Mediates Tumor Suppression in Hepatocellular Carcinoma.

Many post-transcriptional mRNA processing steps play crucial roles in tumorigenesis and the progression of cancers, such as N6-methyladenosine (m6A) modification and alternative splicing. Upregulation of methyltransferase-like 3 (METTL3), the catalytic core of the m6A methyltransferase complex, increases m6A levels and results in significant effects on the progression of hepatocellular carcinoma (HCC). However, alternative splicing of METTL3 has not been fully investigated, and the functions of its splice variants remain unclear. Here, we analyzed both our and online transcriptomic data, obtaining 13 splice variants of METTL3 in addition to canonical full-length METTL3-A in HCC cell lines and tissues. Validated by RT-qPCR and Western blotting, we found that METTL3-D, one of the splice variants expressing a truncated METTL3 protein, exhibits higher levels than METTL3-A in normal human livers but lower levels than METTL3-A in HCC tumor tissues and cell lines. Further functional assays demonstrated that METTL3-D expression decreased cellular m6A modification, inhibited the proliferation, migration, and invasion of HCC cells, and was negatively associated with the malignancy of patient tumors, exhibiting functions opposite to those of full-length METTL3-A. This study demonstrates that the METTL3-D splice variant is a tumor suppressor that could potentially be used as a target for HCC therapy.

Risk factors for post-traumatic stress disorder after emergency trauma surgery / 中华麻醉学杂志

Objective:To screen the risk factors for post-traumatic stress disorder (PTSD) after emergency trauma surgery in the patients.Methods:The medical records of emergency surgical trauma patients (traffic accident, fall, engineering accident, etc.) were retrospectively collected.The general condition and perioperative clinical indicators of the patients were recorded.The patients were divided into PTSD group and non-PTSD group according to whether PTSD occurred within 1 month after surgery.Multivariate logistic regression analysis was used to screen the risk factors for PTSD.Results:A total of 312 patients were enrolled, and the incidence of PTSD at 1 month after surgery was 19.9%.There were significant differences in preoperative VAS score, ratio of gender, intraoperative use of propofol, intraoperative use of dexmedetomidine, and postoperative ICU transfer rate between PTSD group and non-PTSD group ( P<0.05). The results of logistic regression analysis showed that intraoperative use of propofol, preoperative high VAS score and postoperative admission to ICU were independent risk factors for PTSD, and intraoperative use of dexmedetomidine was a protective factor for the prevention of PTSD ( P<0.05). Conclusions:Intraoperative use of propofol, preoperative high VAS score and postoperative transfer to ICU are independent risk factors for postoperative PTSD in the patients with emergency trauma, and intraoperative use of dexmedetomidine is a protective factor for the prevention of PTSD.

Effects of dexmedetomidine on enhancement of fear memory by propofol in rats with post-traumatic stress disorder / 中华麻醉学杂志

Objective:To evaluate the effects of dexmedetomidine on the enhancement of fear memory by propofol in rats with post-traumatic stress disorder (PTSD).Methods:Two hundred and twenty clean-grade healthy male Sprague-Dawley rats, weighing 300-400 g, aged 12-16 weeks, underwent conditioned fear memory training, and PTSD model was developed.One hundred and twenty rats were divided into 6 groups ( n=20 each) by a random number table method: control group (C group), PTSD group, propofol group (P1 group), and propofol + different doses of dexmedetomidine groups (P1+ DEX10 group, P1+ DEX20 group and P1+ DEX40 group). In group C, only sound was played and no electric shock was given during conditioned fear memory training.After conditioned fear memory training, sesame oil 1 ml/kg was intraperitoneally injected in PTSD group, propofol 1 ml/kg was intraperitoneally injected in group P1, and dexmedetomidine 10, 20 and 40 μg/kg were intraperitoneally injected in P1+ DEX10, P1+ DEX20 and P1+ DEX40 groups, respectively.After drug administration, conditioned fear memory test was performed to record the time of rigid behavior within 90 s, and the percentage of time of rigid behavior was calculated.The development of SpO 2<90% was recorded during administration.One hundred Sprague-Dawley rats were divided into 5 groups ( n=20 each) by the random number table method: propofol group (P2 group), and propofol+ dexmedetomidine given at different timings groups (P2+ DEX T0 group, P2+ DEX T30 group, P2+ DEX T60 group and P2+ DEX T90 group). After the conditioned fear memory training, propofol 1 ml/kg was intraperitoneally injected in 5 groups, an then dexmedetomidine 20 μg/kg was intraperitoneally injected at 0, 30, 60 and 90 min after propofol administration in P2+ DEX T0, P2+ DEX T30, P2+ DEX T60 and P2+ DEX T90 groups, respectively.Conditioned fear memory test was performed after drug administration to record the time of rigid behavior within 90 s, and the percentage of time of rigid behavior was calculated. Results:Only 6 rats developed SpO 2<90% during the administration period in P1+ DEX40 group.Compared with C group, the percentage of time of rigid behavior was significantly increased in PTSD group ( P<0.05). Compared with PTSD group, the percentage of time of rigid behavior was significantly increased in P1 group ( P<0.05). Compared with P1 group, the percentage of time of rigid behavior was significantly decreased in P1+ DEX20 and P1+ DEX40 groups ( P<0.05), and no significant change was found in the percentage of time of rigid behavior in P1+ DEX10 group ( P>0.05). Compared with P2 group, the percentage of time of rigid behavior was significantly decreased in P2+ DEX T0 and P2+ DEX T30 groups ( P<0.05), and no significant change was found in the percentage of time of rigid behavior in P2+ DEX T60 and P2+ DEX T90 groups ( P>0.05). Conclusions:Dexmedetomidine can attenuate propofol-induced enhancement of fear memory in a rat model of PTSD, and the best effect is achieved in early administration of moderate dose (20 μg/kg, within 30 min after propofol administration).

A cross-sectional study of olfactory and taste disorders among COVID-19 patients in China.

To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.

Clinical outcomes and patterns of failure of head and neck mucosal melanoma treated with multiple treatment modalities.

OBJECTIVES: The study aims to analyze the clinical characteristics of head and neck mucosal melanoma (MMHN) and the effects of multiple treatment modalities on distant metastasis, recurrence and survival rates to provide a reference for the individualized treatment of MMHN. METHODS: We retrospectively reviewed 262 patients with stage III-IVb MMHN treated from March 1986 to November 2018 at our cancer center. RESULTS: The median follow-up time was 34.0 months (range 1-262 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) probabilities were 37.7%, 30.2%, and 20.3%, respectively. The 5-year OS rates for patients with stage III, stage IVA, and stage IVB MMHN were 67.0%, 24.1% and 8.3%, respectively (P < 0.001). A total of 246 (93.9%) patients received surgery, 149 (56.9%) patients received chemotherapy, and 69 (26.3%) patients received immunologic/targeted therapy. A total of 106 (40.5%) patients were treated with radiotherapy: 9 were treated with preoperative radiotherapy, 93 were treated with postoperative radiotherapy, and 4 were treated with radiotherapy alone. In the multivariate Cox regression analysis, primary tumor site, T stage, and immunologic/targeted therapy were independent factors for OS (all P < 0.05). Irradiation technique, T stage, and N stage were independent prognostic factors for DMFS (all P < 0.05). T stage, N stage, and surgery were independent prognostic factors for DFS (all P < 0.05). Distant metastasis was observed in 107 of 262 patients (40.8%), followed by local [74 (28.2%)] and regional [52 (19.8%)] recurrence. CONCLUSIONS: The main reason for treatment failure in MMHN is distant metastasis. Immunologic/targeted therapy and surgery are recommended to improve the survival of MMHN. The American Joint Committee on Cancer (AJCC) 8th edition staging system for MMHN does stage this disease effectively.

Unconventional Pyridyl Ligand Inclusion within a Flexible Metal-Organic Framework Bearing an N,N'-Diethylformamide (DEF)-Solvated Cd5 Cluster Secondary Building Unit.

A cationic three-dimensional (3D) metal-organic framework (MOF) sustained by an N,N'-diethylformamide (DEF)-solvated zigzag-shaped Cd5 cluster secondary building unit (SBU), [Et2 NH2 ]2 [Cd5 (BTB)4 (DEF)2 ] ⋅ 4.75DEF (1 a, H3 BTB=benzene-1,3,5-tribenzoic acid) shows flexible framework behavior and undergoes solvate exchange with CHCl3 to yield [Et2 NH2 ]2 [Cd5 (BTB)4 (DEF)2 ] ⋅ xCHCl3 (1 b) accompanied by changes to pore sizes and shapes. Unexpectedly, the DEF solvates coordinated to the central Cd2+ could not be replaced by strongly donor pyridyl and dipyridyl ligands. Additionally, more electron-deficient pyridyls preferentially coordinated to the flanking Cd2+ of the Cd5 SBU, as exemplified by [Et2 NH2 ]2 [Cd5 (BTB)4 (DEF)2 (PyCHO)2 ] ⋅ xSol (2 a, PyCHO=4-pyridinealdehyde) and [Et2 NH2 ]2 [Cd5 (BTB)4 (DEF)2 (PyAc)2 ] ⋅ xSol (2 b, PyAc=4-acetylpyridine). Density functional theory (DFT) calculations were used to understand these counterintuitive observations.

Berberine mitigates high glucose-induced podocyte apoptosis by modulating autophagy via the mTOR/P70S6K/4EBP1 pathway.

AIMS: This study aimed to investigate the characteristics and mechanism of autophagy on podocyte apoptosis under high glucose (HG) conditions and further explore the effect of berberine on podocyte autophagy, apoptosis and the potential mechanism. MATERIALS AND METHODS: The levels of LC3II/I in podocytes stimulated with HG were detected at 0, 2, 4, 8, 12, 24, 36 and 48 h by western blotting. CCK-8 was used to detect the viability of podocytes. The level of autophagy was detected by western blotting, transmission electron microscopy and immunofluorescence. Podocyte apoptosis was analysed by using Hoechst staining, western blotting, annexin V/propidium iodide dual staining, and confocal microscopy. Then, podocytes were transfected with siRNA to silence mTOR, and the expression levels of proteins and mRNA involved in the mTOR/P70S6K/4EBP1 pathway were further investigated by western blotting and qRT-PCR. KEY FINDINGS: In this study, we found significantly reduced LC3II/LC3I and increased p62 in podocytes stimulated with HG for 24 h, and the level of autophagy reached a minimum at 24 h. Berberine restored podocyte viability and significantly attenuated HG-mediated inhibition of autophagy, as evidenced by the increased expression of LC3II/LC3I, the number of autophagosomes and the inhibition of p62. Moreover, berberine counteracted HG-induced podocyte apoptosis and injury, which was negatively correlated with the autophagy effect. Notably, silencing mTOR with siRNA augmented the inhibition of P70S6k and 4EBP1 phosphorylation, which was similar to the effect of berberine. SIGNIFICANCE: Berberine activates podocyte autophagy by inhibiting the mTOR/P70S6K/4EBP1 signaling pathway, thereby alleviating podocyte apoptosis.

Clinical study on Jin's three-needle therapy for post-stroke cognitive impairment / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of Jin's three-needle therapy on post-stroke cognitive impairment (PSCI) and the effect on neuroelectrophysiology (event-related potentials). Methods: A total of 60 PSCI patients were selected and divided into a treatment group and a control group according to the method of random number table, with 30 cases in each group. The patients in the control group received routine treatment while the patients in the treatment group received additional Jin's three-needle therapy. The treatment for both groups lasted four weeks. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores as well as amplitude and latency of potential 300 (P300) were adopted to compare the between-group results before and after treatment. Results: Before treatment, there were no significant differences (all P>0.05) in MMSE and MoCA scores, P300 latency and P300 amplitude between the two groups. After 4 weeks of treatment, the MMSE and MoCA scores and P300 amplitudes were improved in both groups, and the P300 latencies became shorter. The results showed significant intra-group and between-group differences (all P<0.05). Conclusion: Based on the routine treatment, Jin's three-needle therapy is effective for PSCI. The mechanism is probably through its regulation on the patients' neuroelectrophysiology.

Comparison of the effect of traditional hysteroscopy and HEOS system hysteroscopy in the treatment of refractory intrauterine residual / 中国基层医药

Objective To compare the clinical effects of conventional hysteroscopy and HEOS hysteroscopy in the treatment of refractory intrauterine residuals.Methods From January 2017 to February 2019,60 patients with refractory intrauterine pregnancy residuals admitted to the Integrated Traditional Chinese and Western MedicineHospital of Wenzhou were randomly selected .The patients were divided into traditional endoscopy group and HEOS system endoscope group according to the different operation method ,with 30 cases in each group.The operation time, intraoperative blood loss , hospitalization cost , postoperative uterine adhesion rate , postoperative menstrual recovery time,postoperative recovery rate of endometrium at the first ,second and third month after operation were compared between the two groups.Results The operation time of the conventional laparoscopic group was (24.38 ±3.16)min, which was longer than that of the HEOS system hysteroscopy group [(18.71 ±3.32)min](t=1.336,P=0.027). The intraoperative blood loss of the conventional laparoscopic group was (18.41 ±4.35) mL,which was higher than that of the HEOS system hysteroscopy group[(12.81 ±3.84)mL](t=1.853,P=0.031).The hospitalization cost of the conventional laparoscopic group was (7461.87 ±344.92) CNY,which was more than that of the HEOS system hysteroscopy group[(6743.19 ±298.52)CNY](t=0.037,P=0.040).In addition,the uterine adhesion rate in the traditional hysteroscopic group was 20.00％( 6/30 ) , which was higher than that in the HEOS system hysteroscopy group[6.67％(2/30)] (χ2 =2.308,P=0.029),and the postoperative menstrual recovery time in the traditional hysteroscopic group was ( 31.46 ±4.12 ) d, which was longer than that in the HEOS system hysteroscopy group [(26.18 ±3.72)d](t=1.730,P=0.026).At the first,second and third month after operation ,the good endometrial recovery rates in the traditional laparoscopic group were 20.00％(6/30),43.33％(13/30),63.33％(19/30), respectively,which were lower than those in the HEOS system hysteroscopy group [46.67％(14/30),70.00％(21/30),93.33％(28/30)](χ2 =4.800,4.344,7.954,P =0.028,0.037,0.005).Conclusion HEOS system endoscope in the treatment of refractory intrauterine residual has good effect and is worthy of promoting .

Comparison of the effect of traditional hysteroscopy and HEOS system hysteroscopy in the treatment of refractory intrauterine residual / 中国基层医药

Objective@#To compare the clinical effects of conventional hysteroscopy and HEOS hysteroscopy in the treatment of refractory intrauterine residuals.@*Methods@#From January 2017 to February 2019, 60 patients with refractory intrauterine pregnancy residuals admitted to the Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou were randomly selected.The patients were divided into traditional endoscopy group and HEOS system endoscope group according to the different operation method, with 30 cases in each group.The operation time, intraoperative blood loss, hospitalization cost, postoperative uterine adhesion rate, postoperative menstrual recovery time, postoperative recovery rate of endometrium at the first, second and third month after operation were compared between the two groups.@*Results@#The operation time of the conventional laparoscopic group was (24.38±3.16)min, which was longer than that of the HEOS system hysteroscopy group[(18.71±3.32)min](t=1.336, P=0.027). The intraoperative blood loss of the conventional laparoscopic group was (18.41±4.35)mL, which was higher than that of the HEOS system hysteroscopy group[(12.81±3.84)mL](t=1.853, P=0.031). The hospitalization cost of the conventional laparoscopic group was (7 461.87±344.92)CNY, which was more than that of the HEOS system hysteroscopy group[(6 743.19±298.52)CNY](t=0.037, P=0.040). In addition, the uterine adhesion rate in the traditional hysteroscopic group was 20.00%(6/30), which was higher than that in the HEOS system hysteroscopy group[6.67%(2/30)](χ2=2.308, P=0.029), and the postoperative menstrual recovery time in the traditional hysteroscopic group was (31.46±4.12)d, which was longer than that in the HEOS system hysteroscopy group[(26.18±3.72)d](t=1.730, P=0.026). At the first, second and third month after operation, the good endometrial recovery rates in the traditional laparoscopic group were 20.00%(6/30), 43.33%(13/30), 63.33%(19/30), respectively, which were lower than those in the HEOS system hysteroscopy group[46.67%(14/30), 70.00%(21/30), 93.33%(28/30)](χ2=4.800, 4.344, 7.954, P=0.028, 0.037, 0.005).@*Conclusion@#HEOS system endoscope in the treatment of refractory intrauterine residual has good effect and is worthy of promoting.

Curcumin Inhibits the Proliferation, Migration, Invasion, and Apoptosis of Diffuse Large B-Cell Lymphoma Cell Line by Regulating MiR-21/VHL Axis

ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. Mechanistically, CD36-mediated oxLDL uptake triggers CEBPß expression to directly upregulate Nogo-B, which interacts with ATG5 to promote lipophagy leading to lysophosphatidic acid-enhanced YAP oncogenic activity. This CD36-Nogo-B-YAP pathway consequently reprograms oxLDL metabolism and induces carcinogenetic signaling for NAFLD-associated HCCs. Targeting the Nogo-B pathway may represent a therapeutic strategy for HCC arising from the metabolic syndrome.

Vaccinia Virus BBK E3 Ligase Adaptor A55 Targets Importin-Dependent NF-κB Activation and Inhibits CD8+ T-Cell Memory.

Viral infection of cells is sensed by pathogen recognition receptors that trigger an antiviral innate immune response, and consequently viruses have evolved countermeasures. Vaccinia virus (VACV) evades the host immune response by expressing scores of immunomodulatory proteins. One family of VACV proteins are the BTB-BACK (broad-complex, tram-trac, and bric-a-brac [BTB] and C-terminal Kelch [BACK]) domain-containing, Kelch-like (BBK) family of predicted cullin-3 E3 ligase adaptors: A55, C2, and F3. Previous studies demonstrated that gene A55R encodes a protein that is nonessential for VACV replication yet affects viral virulence in vivo Here, we report that A55 is an NF-κB inhibitor acting downstream of IκBα degradation, preventing gene transcription and cytokine secretion in response to cytokine stimulation. A55 targets the host importin α1 (KPNA2), acting to reduce p65 binding and its nuclear translocation. Interestingly, while A55 was confirmed to coprecipitate with cullin-3 in a BTB-dependent manner, its NF-κB inhibitory activity mapped to the Kelch domain, which alone is sufficient to coprecipitate with KPNA2 and inhibit NF-κB signaling. Intradermal infection of mice with a virus lacking A55R (vΔA55) increased VACV-specific CD8+ T-cell proliferation, activation, and cytotoxicity in comparison to levels of the wild-type (WT) virus. Furthermore, immunization with vΔA55 induced increased protection to intranasal VACV challenge compared to the level with control viruses. In summary, this report describes the first target of a poxvirus-encoded BBK protein and a novel mechanism for DNA virus immune evasion, resulting in increased CD8+ T-cell memory and a more immunogenic vaccine.IMPORTANCE NF-κB is a critical transcription factor in the innate immune response to infection and in shaping adaptive immunity. The identification of host and virus proteins that modulate the induction of immunological memory is important for improving virus-based vaccine design and efficacy. In viruses, the expression of BTB-BACK Kelch-like (BBK) proteins is restricted to poxviruses and conserved within them, indicating the importance of these proteins for these medically important viruses. Using vaccinia virus (VACV), the smallpox vaccine, we report that the VACV BBK protein A55 dysregulates NF-κB signaling by disrupting the p65-importin interaction, thus preventing NF-κB translocation and blocking NF-κB-dependent gene transcription. Infection with VACV lacking A55 induces increased VACV-specific CD8+ T-cell memory and better protection against VACV challenge. Studying viral immunomodulators therefore expands not only our understanding of viral pathogenesis and immune evasion strategies but also of the immune signaling cascades controlling antiviral immunity and the development of immune memory.

Diagnostic value of serum NSE, S100B protein and myocardial zymogram in premature infants with intrauterine infection / 中国基层医药

Objective@#To explore the diagnostic value of serum NSE, S100B protein and myocardial zymogram in premature infants with intrauterine infection.@*Methods@#From January 2016 to December 2017, 60 preterm infants with intrauterine infection in the Integrated Chinese and Western Medicine Hospital of Wenzhou were selected in the study.According to whether brain injury occurred, they were divided into brain injury group (28 cases) and non-brain injury group (32 cases). Serum NSE content was detected by chemiluminescence method, serum S100B protein level was detected by enzyme linked immunosorbent assay (ELISA), and serum CK and HBDH levels were detected by automatic biochemical analyzer.The serum levels of NSE, S100B, CK and HBDH were compared between the two groups, the combined diagnostic efficacy of NSE+ S100B protein+ CK+ HBDH was analyzed, the correlation of serum NSE, S100B protein, CK, HBDH with brain injury wasanalyzed.@*Results@#The levels of serum NSE [(2.43±0.54)μg/L] and S 100B [(14.36±3.21)ng/L] in the brain injury group were higher than those in the non-brain injury group [(0.97±0.27)μg/L and (8.10±1.87)ng/L] (t=13.498, 9.370, all P<0.05). The levels of serum CK [(437.64±54.12)U/L] and HBDH [(387.91±56.45)U/L] in the brain injury group were significantly higher than those in the non-brain injury group [(183.54±32.58)U/L and (174.3±26.63)U/L] (t=22.347, 19.126, all P<0.05). The sensitivity and specificity of the combined diagnosis of NSE+ S100B protein and myocardial zymogram were higher than those of each single index.Serum NSE, S100B protein, CK and HBDH were positively correlated with brain injury.@*Conclusion@#The elevation of serum NSE, S100B protein and myocardial zymogram in preterm infants with intrauterine infection after birth has certain clinical significance in judging whether brain injury occurs or not.