Added value of shear-wave elastography in the prediction of extracapsular extension and seminal vesicle invasion before radical prostatectomy / 亚洲男科学杂志(英文版)

The purpose of this study was to analyze the value of transrectal shear-wave elastography (SWE) in combination with multivariable tools for predicting adverse pathological features before radical prostatectomy (RP). Preoperative clinicopathological variables, multiparametric magnetic resonance imaging (mp-MRI) manifestations, and the maximum elastic value of the prostate (Emax) on SWE were retrospectively collected. The accuracy of SWE for predicting adverse pathological features was evaluated based on postoperative pathology, and parameters with statistical significance were selected. The diagnostic performance of various models, including preoperative clinicopathological variables (model 1), preoperative clinicopathological variables + mp-MRI (model 2), and preoperative clinicopathological variables + mp-MRI + SWE (model 3), was evaluated with area under the receiver operator characteristic curve (AUC) analysis. Emax was significantly higher in prostate cancer with extracapsular extension (ECE) or seminal vesicle invasion (SVI) with both P < 0.001. The optimal cutoff Emax values for ECE and SVI were 60.45 kPa and 81.55 kPa, respectively. Inclusion of mp-MRI and SWE improved discrimination by clinical models for ECE (model 2 vs model 1, P = 0.031; model 3 vs model 1, P = 0.002; model 3 vs model 2, P = 0.018) and SVI (model 2 vs model 1, P = 0.147; model 3 vs model 1, P = 0.037; model 3 vs model 2, P = 0.134). SWE is valuable for identifying patients at high risk of adverse pathology.

Multiparametric ultrasound for the assessment of testicular lesions with negative tumoral markers / 亚洲男科学杂志(英文版)

The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.

Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy / 亚洲男科学杂志(英文版)

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Molecular genetic characterization of Blastocystis in primary and middle school students in Baisha Li Autonomous County, Hainan / 中国热带医学

@#Abstract: Objective　To investigate the prevalence and genetic characterization of Blastocystis in primary and middle school students in Baisha Li Autonomous County, Hainan Province, in order to understand the infection status of Blastocystis and its subtype distribution characteristics in this area. Methods　From March to November 2021, fecal samples were collected from two primary and middle schools in Baisha Li Autonomous County. Nested PCR targeting the SSU rDNA was employed in this study, sequence analysis were performed to determine the prevalence and subtype. A neighbor-joining tree was built using Mega 7. Meanwhile, the risk factors of the Blastocystis infection among different grades and genders were evaluated. Results　The infection rate of Blastocystis was 4.1% (13/314), there was no statistical difference in infection rates among genders and grades (P>0.05). Sequence analysis revealed that three Blastocystis subtypes were identified, namely ST3 (n=7), ST7 (n=4) and ST1 (n=2), all of which have zoonotic potential. Conclusions　This is the first report of the identification of Blastocystis in humans in Hainan at the subtype level, and provide the basic data for the prevention and control of Blastocystis in this area. The zoonotic subtypes identified in this area indicated more studies should be taken in humans and various animals, to better evaluate the transmission of Blastocystis and provide scientific support for the prevention and control of Blastocystis.

Clinicopathological features of mature T/NK cell lymphoma with aberrant CD20 or CD79α expression / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics and prognosis of mature T/NK cell lymphomas with aberrant CD20 or CD79α expression. Methods: A retrospective analysis of 641 cases of mature T/NK cell lymphoma diagnosed from January 2014 to December 2020 was performed, and 14 cases of CD20-positive and one case of CD79α-positive mature T/NK-cell lymphoma were identified. Histological examination, immunohistochemical characterization, in situ hybridization for Epstein-Barr virus encoded early RNA (EBER), and PCR testing for immunoglobulin and T cell receptor (TCR) gene rearrangements were performed. Clinicopathological characteristics of these lymphomas were analyzed. Results: There were 13 males and 2 females, with a median age of 56 years. There were 8 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 3 cases of extranodal NK/T-cell lymphoma, nasal type (ENKTCL), 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and 2 cases of angioimmunoblastic T-cell lymphoma (AITL). Twelve cases were stage Ⅲ or Ⅳ lymphomas. The prognosis was overall poor. The histology, immunophenotype and TCR gene rearrangement were not significantly different from the corresponding types of lymphoma. Ki-67 proliferation index was over 70% in all cases. The expression of CD20 or CD79α was weak and heterogeneous. All 15 case of Ig gene rearrangement were polyclonal. Conclusions: Mature T/NK cell lymphoma with abnormal expression of CD20 or CD79α is rare, commonly found in advanced stage, and associated with poor prognosis. The expression of CD20 or CD79α in these cases is weaker than the corresponding mature T/NK cell lymphomas, while its proliferation index is higher. Histomorphology, extensive immunoprofiling and molecular detection are required for accurate diagnosis.

Clinicopathological features and BRAF V600E and MYD88 L265P mutation status of nodal marginal zone lymphoma / 中华病理学杂志

Objective: To investigate the clinicopathological features as well as BRAF V600E and MYD88 L265P mutation status of nodal marginal zone B cell lymphoma (NMZL). Methods: Thirty-two cases of NMZL were diagnosed from September 2009 to February 2021 at the Henan Provincial People's Hospital and Peking University School of Basic Medical Sciences. The clinicopathologic characteristics were obtained and analyzed. BRAF V600E and MYD88 L265P mutation status were identified using PCR and Sanger sequencing, respectively. Results: There were 20 males and 12 females patients with a median age of 69 years (ranging 36-82 years). The most prevalent clinical manifestation was multiple lymph nodes enlargement in head and neck (22/32, 68.8%), followed by inguinal (12/32, 37.5%), axillary (11/32, 34.4%), mediastinum (5/32, 15.6%) and retroperitoneal lymph nodes (4/32, 12.5%). Most of the patients were in Ann Arbor stage Ⅰ/Ⅱ (21 cases). The morphologic features included diffuse (24/32, 75.0%), nodular (5/32, 15.6%), interfollicular (2/32,6.3%) and perifollicular (1/32,3.1%) types. The tumor cells showed monocyte-like, centrocyte-like, small lymphocyte-like and plasma cell-like differentiation. Immunophenotyping revealed diffuse expression of CD20 in all tumor cells, whereas CD43 (11/32, 34.4%), bcl-2 (20/32, 62.5%), MNDA (13/32, 40.6%) and CD5 (2/32, 6.3%) were partially expressed. Ki-67 proliferation index varied from 10% to 40%. BRAF V600E mutation was found in two cases (2/32, 6.3%), but MYD88 L265P mutation was not detected. Eighteen patients survived and three died at the end of follow-up period which ranged 6 to 110 months. Conclusions: The morphologic features of NMZL varies across individuals, it should be differentiated from various B-cell lymphomas; however immunological biomarkers with high specificity for NMZL are still lacking. No MYD88 L265P mutation is found in NMZL. Some cases may harbor BRAF V600E mutation and yet the prevalence remains indeterminate; further researches are warranted.

Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis / 南方医科大学学报

OBJECTIVE@#To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism.@*METHODS@#Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas.@*RESULTS@#Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05).@*CONCLUSION@#The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Contractile Properties of Erector Spinae in Patients with Chronic Nonspecific Low Back Pain: Based on Tensiomyography / 中国康复理论与实践

Objective:To analyze the contractile properties of the lumbar erector spinae in patients with chronic nonspecific low back pain (CNLBP), and to explore their correlation with pain and dysfunction. Methods:From January to June, 2020, 24 patients with CNLBP in the outpatient and the ward of geriatric rehabilitation medicine department and 26 asymptomatic volunteers were included. Their contractile properties of the lumbar erector spinae were measured with tensiomyography, including maximum radial muscle displacement (Dm), contraction time (Tc), delay time (Td), sustain time (Ts), half-time relaxation (Tr) and lateral symmetry (LS). The contraction velocity (VC) was calculated. Potential associations of tensiomyography parameters to Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed using correlation analysis. Results:No significant differences were found in Td, Ts, Tc, Tr and LS between two groups (P > 0.05). Dm and Vc were significantly lower in both sides of CNLBP group than in the control group (t > 2.058, P < 0.01). Dm or Vc were not correlated with VAS and ODI (P > 0.05). Conclusion:Erector spinae are stiff and fatiguable in patients with CNLBP, however, they are not associated with pain and dysfunction. Tensiomyography could be used for accurate diagnosis and treatment of CNLBP.

Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity / 医学前沿

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

New effect of G-protein coupled receptors on blood pressure regulation / 中国中药杂志

Hypertension is a clinical syndrome characterized by elevated systemic arterial blood pressure, which may be accompanied by functional or organic damage of heart, brain, kidney and other organs. The pathogenesis and development of hypertension are affected by genetic, environmental, epigenetic, intestinal microbiota and other factors. They are the result of multiple factors that promote the change of blood pressure level and vascular resistance. G protein coupled receptors(GPCRs) are the largest and most diverse superfamily of transmembrane receptors that transmit signals across cell membranes and mediate a large number of cellular responses required by human physiology. A variety of GPCRs are involved in the control of blood pressure and the maintenance of normal function of cardiovascular system. Hypertension contributes to the damages of heart, brain, kidney, intestine and other organs. Many GPCRs are expressed in various organs to regulate blood pressure. Although many GPCRs have been used as therapeutic targets for hypertension, their efficacy has not been fully studied. The purpose of this paper is to elucidate the role of GPCRs in blood pressure regulation and its distribution in target organs. The relationship between GPCRs related to intestinal microorganisms and blood pressure is emphasized. It is proposed that traditional Chinese medicine may be a new way to treat hypertension by regulating the related GPCRs via intestinal microbial metabolites.

Comparative study on the effects of total ginkgo flavonol glycosides and total ginkgolides on neurofunctional recovery in mice with subacute stroke / 药学学报

As a Ginkgo biloba extract preparation, shuxuening injection has a unique advantage in the prevention and treatment of acute and subacute stroke, but its main active ingredient is still unclear. Using a subacute model of stroke in mice constructed earlier, we further explored the contribution and mechanism of the two main components of total ginkgo flavonol glycosides and total ginkgolides in facilitating the neurofunctional recovery in stroke-induced mice. The pharmacodynamics was mainly evaluated by neurobehavioral changes, cerebral infarction volume, blood-brain barrier permeability and brain edema. The pathway and targets were predicted by transcriptome and network pharmacology. Finally, the mechanism was verified at the mRNA and protein levels. The results showed that the beneficial effect of total ginkgolides was greater than that of total ginkgo flavonol glycosides in both the pharmacodynamics and the regulatory mechanism of granulocyte adhesion and diapedesis involving granulocyte colony-stimulating factor (G-CSF), macrophage-1 antigen (MAC-1) and E-selectin. These findings suggest that shuxuening injection may improve the prognosis for mice with subacute stroke by down-regulating G-CSF-mediated granulocyte adhesion and diapedesis pathway mainly through the total ginkgolide components. This finding is expected to provide reference for optimizing prescription and searching for natural drugs for targeting the treatment of ischemic stroke prognosis. The animal experiments in this study followed the regulations of Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine.

Calcifying fibrous tumor: a clinicopathological analysis of 32 cases / 中华病理学杂志

To investigate the clinicopathological characteristics, histogenesis, immunophenotypes, molecular genetic characteristics, diagnosis and differential diagnosis of calcifying fibrous tumors (CFT). A total of 32 cases of CFT (22 cases from Henan Provincial People's Hospital and 10 cases from PLA Army Medical Center) diagnosed between June 2009 and February 2019 were reviewed. The clinical and pathologic data were analyzed. There were 12 male and 20 female patients, aged from 15 to 63 years (mean 40.8 years). Eleven cases occurred in stomach, four cases in retroperitoneum, four cases in ovary, two cases in scrotum, two cases in mediastinum, two cases in head and neck, one case each in thoracic cavity, lung, adrenal gland, kidney, sigmoid colon, epididymis and mesosalpinx. All the tumors were solid masses with clear boundaries. The maximal dimension of the tumors ranged from 0.6 to 10.0 cm. Microscopically, there was hypocellular stromal sclerosis and wavy storiform coarse collagen with superimposed scattered or patchy lymphocytes and plasma cells; calcification or gravel formation were also detected. Immunohistochemistry showed that spindle cells were positive for vimentin and some were positive for CD34; and they were negative for calponin, SMA, desmin, S-100 protein, SOX10, STAT6, β-catenin, ALK, CD117, DOG1, CKpan, and EMA. No ALK rearrangement was detected by FISH in all cases. No C-KIT and PDGFRA mutation was detected in all the tested 11 cases of stomach, four cases of retroperitoneal and one case of sigmoid colon CFT. MDM2 was not amplified by FISH in all four tested cases of retroperitoneal CFT. CFT is a rare benign tumor of fibroblastic cell origin. The diagnosis mainly depends on histomorphologic analysis and immunophenotyping. CFT should be differentiated from other benign and malignant spindle cell mesenchymal tumors.

One-stage transpedicular debridement, posterior internal fixation and fusion for the treatment of senile thoracolumbar tuberculosis / 中国骨伤

OBJECTIVE@#To evaluate the clinical outcomes of one-stage transpedicular debridement, posterior internal fixation, RBK mixed streptomycin filled bone grafting for the treatment of elderly patients with thoracolumbar tuberculosis.@*METHODS@#The clinical data of 20 elderly patients with thoracolumbar tuberculosis underwent one stage transpedicular debridement, posterior internal fixation, OSTEOSET RBK mixed streptomycin-filled bone grafting from September 2006 to July 2017 were retrospectively analyzed. There were 12 males and 8 females, aged from 62 to 83 years with an average of (72.4±6.9) years old. Visual analogue scale (VAS), Oswestry Disability Index (ODI)were used to evaluate the pain and spinal function. The kyphosis angle (Cobb angle) of the lesion segment and the bone growth of the lesion area were observed by the X-ray films.@*RESULTS@#All the operations were successful, the operation time was (160.9±23.8) min, and the intraoperative blood loss was (317.9± 112.7) ml. The incisions were healed by first intention, and no sinus and incision were delayed. Spinal tuberculosis was completely cured, Frankel grade has one or more improvements. The VAS score decreased from (7.50±1.15) points before surgery to (1.70±1.39) points at 12 months after surgery (<0.05). The ODI score decreased from preoperative (92.50±1.17)% to (12.80±0.89)% at the final follow up (<0.05). The sagittal Cobb angle of the lesion segment decreased from preoperative (24.2±1.6)° to (8.3±0.7)°at 12 months after surgery(<0.05), the kyphosis deformity was significantly corrected. In all cases, bone fusion was achieved in bone graft area, without bone nonunion and device fracture complications.@*CONCLUSION@#One-stage transpedicular debridement, posterior internal fixation, RBK mixed streptomycin filled bone grafting is suitable for thoracolumbar tuberculosis patients with good general condition and less vertebral destruction.

Relationship between alterations of spine-pelvic sagittal parameters and clinical outcomes after oblique lumbar interbody fusion / 中国骨伤

OBJECTIVE@#To investigate the relationship between spine-pelvic sagittal parameters and clinical efficacy before and after oblique lumbar interbody fusion(OLIF).@*METHODS@#A retrospective analysis of clinical data of 65 patients with lumbar degenerative diseases treated with OLIF were performed from July 2017 to July 2018. There were 26 males and 39 females aged from 33 to 79 years old with an average of (62.72±10.23) years old. Oswestry Disability Index (ODI) and visual analogue scale (VAS) before and at the latest follow up were evaluated. Disc height (DH) and spine- pelvic sagittal parameters of the surgical segment were measured before and at the latest follow- up, including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL). According to the difference of PI-LL, it was judged whether PI and LL match and the patients were grouped, PI-LL ranged from -9° to 9° was set as matching group, and PI-LL less than -9° or larger than 9° was set as mismatching group. The spine-pelvic sagittal parameters were analyzed before and at the latest follow-up of OLIF in patients with lumbar degenerative diseases, and the correlation between changes and clinical efficacy was compared.@*RESULTS@#All patients were followed up from 8 to 20 months with an average of (14.20±3.68) months. Operation time was (91.54±25.97) min, intraoperative blood loss was (48.15±10.14) ml, and the hospitalization time ranged from 6 to 19 days with an average of (9.28± 2.50) days. Totally 84 surgical levels, 46 patients were single segment and 19 patients were double segments. VAS and ODI score were improved from (4.88±0.99) point, (67.60±13.73) % preoperatively to (2.85±1.30) points, (30.57±6.48) % at the latest follow-up. There were significant differences in VAS and ODI scores between before and at the latest follow-up. The sagittal parameters of LL, PT, SS, PI, PI -LL and the surgical level DH were (42.80 ±16.35)° , (23.22 ±10.91)° , (26.95 ± 13.30)°, (50.22±14.51)°, (7.53±16.13) °, (0.91±0.29) cm preoperatively and improved to the latest follow-up (49.95± 12.82) °, (17.94±9.24) °, (33.71±12.66) °, (51.65±10.26) °, (1.68±17.00) °, (1.20±0.40) cm;there were statistical differences in LL, PT, SS, PI-LL, DH before operation and at the latest follow up, while no difference in PI. LL of preoperative PI-LL in matched group was (48.76±11.09)° , and (38.00±18.37)° in PI-LL mismatch group, there was difference between two groups. There were no differences in VAS, ODI, PT, SS, PI and DH between two groups. At the latest follow-up, ODI between PI-LL matched group and PI-LL mismatched group were (29.40±5.93)% and (32.86±7.02)% respectively, and had difference in ODI between two groups;while there were no significant differences in VAS, LL, PT, SS, PI, and DH. Pearson correlation analysis showed preoperative PT-LL was positively correlated with VAS;PT was positively correlated with ODI at the latest follow-up.@*CONCLUSION@#OLIF has a good surgical effect on lumbar degenerative diseases, and could change spine-pelvic sagittal parameters of patient to a certain extent, and further restoring the balance of the sagittal plane of lumbar spine.

Erratum: Author correction to 'Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome' Acta Pharmaceutica Sinica B 9 (2019) 734-744

[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].

Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

Exploring molecular mechanisms of anti-platelet adhesion of Chinese medicine for promoting blood circulation and removing blood stasis by activity screen and network analysis / 药学学报

Platelet adhesion is a key process in thrombosis. Anti-platelet adhesion effect of some Chinese medicines for promoting blood circulation and removing blood stasis (PBCRBS) has been reported, but their relative efficacies as a whole and specific targets remained unclear. This paper combined activity screening, drug compatibility analysis, pathway clustering, target prediction, and molecular docking to explore the mechanism of anti-platelet adhesion by PBCRBS Chinese medicine. Screening the activity of anti-platelet adhesion of 58 commercially available PBCRBS Chinese patent medicines showed that about 50.0% significantly inhibit ADP-induced platelet adhesion in vitro, and about 96.6% significantly inhibit thrombin-induced platelet adhesion in vitro. The animal experiment involved was approved by the Animal Ethics Committee of Tianjin International Biomedical Research Institute. Combined with the auxiliary platform for TCM (V2.0) inheritance showed that the compatibility of Danshen-Chuanxiong was used most frequently among the top 20 active proprietary Chinese patent medicines. IPA network analysis revealed that IL-1, APP and CCL2 might be the key targets for anti-platelet adhesion function of Danshen-Chuanxiong against atherosclerosis, neuroinflammation and chemokine signaling pathways as the main mechanisms. Molecular docking analysis confirmed the interaction between one of the active compounds shared by Danshen and Chuanxiong, i.e. chlorogenic acid, with its target CCL2. This study provides TCM theory guidance and experimental support for targeting platelet adhesion in anti-thrombosis therapy by Chinese medicine for promoting blood circulation and removing blood stasis.

Idiosyncratic hepatotoxicity evaluation of Cortex Dictamni based on immune stress / 药学学报

Using the idiosyncratic lipopolysaccharide (LPS)-mediated hepatotoxicity model as a positive control, liver injury induced by Cortex Dictamni aqueous extract (AE) or Cortex Dictamni ethanol extracts (EE) was evaluated. Idiosyncratic hepatotoxicity model was established in rats [Institutional Animal Care and Use Committee (IACUC)-2018-008] by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into 10 groups. The plasma levels of liver function biomarkers such as alanine transaminase (ALT), aspartate aminotransferase (AST) were measured. Histological changes (HE staining), hepatocellular apoptosis and the content of cytokines of liver were measured. Network pharmacology was used to analyze the relationship between chemical components and immunity in Cortex Dictamni. Compared with the control group, the doses (25, 50 g·kg-1) of AE or EE had no significant changes in ALT, AST and liver pathology (P>0.05). The doses of 4.2 g·kg-1 of AE or EE+LPS groups exhibited an elevation in ALT, AST and serum cytokines (P<0.01). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in these groups. Network pharmacology shows that Cortex Dictamni may directly or indirectly participate in the process of immunomodulation. We found that Cortex Dictamni regulated 15 core targets and affected 19 pathways, including apoptosis, TNF-α, NF-kappa B signaling pathways. These results suggest that Cortex Dictamni can induce idiosyncratic hepatotoxicity and the water extract can induce more serious liver injury then ethanol extract of Cortex Dictamni. These findings provide a reference for elucidating the idiosyncratic hepatotoxicity induced by Cortex Dictamni.

Effect of enhancer of zeste homolog 2 on the expression of glial cell line-derived neurotrophic factor family receptor α-1 in the colon tissue of children with Hirschsprung's disease / 中国当代儿科杂志

OBJECTIVE@#To study the expression levels of glial cell line-derived neurotrophic factor family receptor α-1 (GFRα1) and enhancer of zeste homolog 2 (EZH2) in the intestinal tissue of children with Hirschsprung's disease (HSCR), as well as the role of EZH2 in the regulation of GFRα1 gene expression and the pathogenesis of HSCR.@*METHODS@#The samples of colon tissue with spasm from 24 children with HSCR after radical treatment of HSCR were selected as the experimental group, and the samples of necrotized colon tissue from 18 children with neonatal necrotizing enterocolitis after surgical resection were selected as the control group. Real-time PCR and Western blot were used to measure the expression levels of GFRα1 and EZH2 in colon tissue in both groups. Human neuroblastoma SH-SY5Y cells were divided into an EZH2 over-expression group and a negative control group. The cells in the EZH2 over-expression group were transfected with pCMV6-EZH2 plasmid, and those in the negative control group were transfected with pCMV6 plasmid. The expression levels of EZH2 and GFRα1 were measured after transfection.@*RESULTS@#Compared with the control group, the experimental group had significant reductions in the mRNA and protein expression levels of GFRα1 and EZH2 in colon tissue (P<0.05), and the protein expression of EZH2 was positively correlated with that of GFRα1 (r=0.606, P=0.002). Compared with the negative control group, the EZH2 over-expression group had significant increases in the expression levels of EZH2 and GFRα1 after SH-SY5Y cells were transfected with EZH2 over-expression plasmid (P<0.05).@*CONCLUSIONS@#Low expression of EZH2 in the colon tissue of children with HSCR may be one of the causes of inadequate expression of GFRα1 and onset of HSCR.

Primary subcutaneous lymphomatous granuloma: a case report and review of literature / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features of primary subcutaneous lymphomatoid granulomatosis (LYG). Methods A case of primary subcutaneous LYG was observed by analysis of the clinical, histological features, immunophenotype and molecular pathology with review of the related literature. Results The male patient, 78-year-old, inadvertently found a mass of right axillary for more than 10 days. The boundary of the mass was clear, it seemed to have a capsule, the cut surface was grayish yellow and grayish red, the texture was medium. A large amount of coagulative necrosis was observed in the center of the mass under microscope. The peripheral area showed a morphological change of panniculitis, accompanied by pleomorphic lymphoid infiltration, showed central and vascular destructive infiltration, pathological mitosis was occasionally observed. Immunophenotyping showed that atypical large lymphoid cells expressed CD45 RB, CD20, CD30, while CD3, CD15, CD56, TIA-1, Granzyme B, ALK, CD21, Langerin and CD1 a, S-100 and CK (AE1/AE3) were negative. The proliferation index of Ki-67 ranged from 50％ to 60％. EBER in situ hybridization showed that positive cells were> 20/HPF.Neither acid fast staining nor TB-DNA testing supported tuberculosis. Molecular pathology found clonal Ig K gene rearrangement, TCRB + TCRG gene rearrangement showed the absence of monoclonal proliferating T cell population. Conclusion The primary subcutaneous LYG is a rare tumor. which can be diagnosed by combination of morphology, immunophenotype and molecular pathology.