Prevention and treatment of lung cancer by regulating tumor-associated macrophages with traditional Chinese medicine / 中国中药杂志

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.

Study on the mechanism of Wuzi-Yanzong-Wan-medicated serum interfering with the mitochondrial permeability transition pore in the GC-2 cell induced by atractyloside / 中国天然药物

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.

Hyperoside protects mouse spermatocytes GC-2 cells from oxidative damage by activating the Keap1/Nrf2/HO-1 pathway / 南方医科大学学报

OBJECTIVE@#To study the protective effect of hyperoside (Hyp) against ydrogen peroxide (H2O2)- induced oxidative damage in mouse spermatocytes GC-2 cells and explore the role of the Keap1/Nrf2/HO-1 pathway in this protective mechanism.@*METHODS@#GC-2 cells were treated with 2.5 mmol/L azaacetylcysteine (NAC), 50, 100, and 200 μmol/L hyperoside, or the culture medium for 48 h before exposure to H2O2 (150 μmol/L) for 2 h. CCK-8 assay was used to detect the changes in cell viability, and cell apoptosis was analyzed using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activity and malondialdehyde (MDA) in the culture medium. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of nuclear factor erythroid 2-related factor2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), and heme oxygenase-1 (HO-1); the nuclear translocation of Nrf2 was detected using immunofluorescence assay.@*RESULTS@#Exposure to H2O2 significantly lowered the proliferation rate, reduced the activities of SOD, GSH and CAT, and obviously increased MDA content, cell apoptosis rate, and the expressions of Keap1 and Nrf2 mRNA and Keap1 protein in GC-2 cells (P < 0.05 or 0.01). Treatment of the cells prior to H2O2 exposure with either NAC or 200 μmol/L hyperoside significantly increased the cell proliferation rate, enhanced the activities of SOD, GSH-PX and CAT, and lowered MDA content and cell apoptosis rate (P < 0.05). Treatment with 200 μmol/L hyperoside significantly decreased the mRNA and protein expressions of Keap1 and increased the expressions of HO-1 mRNA and the protein expressions of Nrf2 and HO-1 (P < 0.05 or 0.01). Hyperoside also caused obvious nuclear translocation of Nrf2 in the cells (P < 0.05).@*CONCLUSION@#Hyperoside protects GC-2 cells against H2O2- induced oxidative damage possibly by activation of the Keap1/Nrf2/HO-1 signaling pathway.

Carbenoxolone enhances inhibitory effect of RSL3 against cisplatin-resistant testicular cancer cells by promoting ferroptosis / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatinresistant testicular cancer cells (I-10/DDP) and the effect of carbenoxolone on the activity of RSL3 against testicular cancer.@*METHODS@#MTT assay was used to evaluate the survival rate of I-10/DDP cells following treatment with RSL3 (1, 2, 4, 8, 16 or 32 μmol/L) alone or in combination with carbenoxolone (100 μmol/L) or after treatment with Fer-1 (2 μmol/L), RSL3 (4 μmol/L), RSL3+Fer-1, RSL3+carbenoxolone (100 μmol/L), or RSL3+Fer-1+carbenoxolone. Colony formation assay was used to assess the proliferation ability of the treated cells; wounding-healing assay and Transwell assay were used to assess the invasion and migration ability of the cells. The expression of GPX4 was detected using Western blotting, the levels of lipid ROS were detected using C11 BODIPY 581/591 fluorescent probe, and the levels of Fe2+ were determined with FerroOrange fluorescent probe.@*RESULTS@#RSL3 dose-dependently decreased the survival rate of I-10/DDP cells, and the combined treatment with 2, 4, or 8 μmol/L RSL3 with carbenoxolone, as compared with RSL3 treatment alone, resulted in significant reduction of the cell survival rate. The combination with carbenoxolone significantly enhanced the inhibitory effect of RSL3 on colony formation, wound healing rate (P=0.005), invasion and migration of the cells (P < 0.001). Fer-1 obviously attenuated the inhibitory effects of RSL3 alone and its combination with carbenoxolone on I-10/DDP cells (P < 0.01). RSL3 treatment significantly decreased GPX4 expression (P=0.001) and increased lipid ROS level (P=0.001) and Fe2+ level in the cells, and these effects were further enhanced by the combined treatment with carbenoxolone (P < 0.01).@*CONCLUSION@#Carbenoxolone enhances the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatin-resistant testicular cancer cells by promoting RSL3-induced ferroptosis.

A case report on demyelinating myelitis occurring after vaccination of freeze-dried human rabies vaccine (Vero cells) / 公共卫生与预防医学

Objective To analyze the suspected case of demyelinating myelitis after vaccination with rabies vaccine (Vero cells) in Yichang city, and to provide a clinical basis for reducing or avoiding similar serious, suspected, and abnormal vaccination reactions after inoculation of rabies vaccine (Vero cells). Methods Epidemiological characteristics of a case of demyelinating myelitis after freeze-dried rabies vaccine (Vero cells) inoculation in Yichang City in 2017 were analyzed. Results In 2017, a case of demyelinating myelitis occurred after inoculation of freeze-dried human rabies vaccine (Vero cells) in Yichang city, which was due to the abnormal reaction of vaccination. Conclusion If abnormal signs occur after vaccination, timely medical treatment should be taken to reduce the occurrence of severe diseases and deaths.

Simultaneous determination and analysis of amino acids and nucleosides in Dendrobium by UHPLC-QTRAP-MS/MS / 中国中药杂志

By using multivariate statistical analysis to evaluate essential quality, and provide scientific basis for their comprehensive utilization, we established an UHPLC-QTRAP-MS/MS method for the fast, precise, efficient determination of 21 kinds of amino acids and 10 kinds of nucleosides in different species of Dendrobium. The analysis was performed on a Waters XBridge Amide column(2.1 mm×100 mm,3.5 μm) with elution by mobile phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow rate of 0.2 mL·min~(-1) with the column temperature at 30 ℃. The target compounds were analyzed by the positive ion multiple reaction monitoring(MRM) mode. The comprehensive evaluation of different species of Dendrobium was carried out by PCA and TOPSIS analysis. All 21 kinds of amino acids and 10 nucleosides showed good linearity among certain concentration range(r>0.999), the RSDs of the stability, precision, and repeatability tests were less than 3.0%. The recovery rate was in the range from 93.31% to 107.5%, and RSD was in the range of 1.1%-3.7%. The comprehensive evaluation index obtained with PCA showed that D. huoshanense was significantly higher than others regarding amino acids and D. officinale has higher nucleosides than other species. The biggest C_i difference of TOPSIS was 68.7%, and comprehensive evaluation showed that D. huoshanense produced the highest comprehensive quality. The method is precise, fast and efficient and can provide reliable basis for further researches and intrinsic quality control of Dendrobium.

Clinical study of sarcopenia and vitamin D deficiency in patients with rheumatoid arthritis and gluco-corticosteroid induced osteoporosis / 中华风湿病学杂志

Objective:To explore the clinical value of sarcopenia and vitamin D deficiency on gluco-corticoid induced osteoporosis (GIOP) in patients with rheumatoid arthritis (RA).Methods:Three hundred and eleven patients with RA from January 2017 to December 2018 were enrolled in the study. One hundred and fifty-eight sex, age-matched normal subjects were recruited as control group. Clinical and laboratory features, daily dosage and treatment duration of glucocorticoid (GC) were recorded in detail. Skeletal muscle mass was measured by biological electrical impedance. Serum levels of 25-hydroxy vitamin D [25(OH)D] were examined using electro-chemiluminescence. Bone mineral density (BMD) at total hip and lumbar vertebra were detected by dual energy X-ray absorptiometry (DEXA). Numerical data and categorical data comparisons were analyzed using χ2 test, non-parametric test, Logistic regression analysis test. Results:① The prevalence of osteoporosis (OP) in RA patients was 33.4%(104/311), which was higher than that in the control group 12.7%(20/158)( χ2=23.267, P<0.01). Percentage of GC taking in 311 RA patients was 56.6%(176/311), and the prevalence of GIOP was 40.9%(72/176). The prevalence of sarcopenia in RA patients was 61.7%(192/311), which was higher than that in the control group [9.0%(14/156), χ2=117.310, P<0.01]. The prevalence of vitamin D deficiency in RA patients was 81.7%(254/311), which was higher than that in control group [38.0%(60/158), χ2=90.415, P<0.01]. ② The prevalence of OP in RA without sarcopenia was 17.6% (21/119), which was lower than that in patients with sarcopenia [43.2%(83/192), χ2=21.601, P<0.01]. In condition without GC, the prevalence of OP in RA without sarcopenia was 9.8%(6/61), which was significantly lower than that in patients with sarcopenia [35.1%(26/74), χ2=11.834, P<0.01]. Under circumstances with GC, the prevalence of OP in RA without sarcopenia (25.9%, 15/58), which was significantly lower than that in patients with sarcopenia (48.3%, 57/118, χ2=8.103, P<0.01). ③ No matter whether existing vitamin D deficiency or not, the prevalence of OP in RA without GC was 23.7%(32/135), which was significantly lower than that in patients with GC [40.9%(72/176), χ2=10.161, P<0.01]. In patients without vitamin D deficiency, the prevalence of OP in RA without GC was 21.4%(6/28), which was similar to that in patients with GC [31.0%(9/29), χ2=0.678, P>0.05]. In the case of vitamin D deficiency, the prevalence of OP in RA without GC was 24.3%(24/107), which was significantly lower than that in patients with GC [42.9% (63/147), χ2=9.370 2, P<0.01]. ④ In RA patients with GC, age( t=5.313, P<0.01), Sharp score ( Z=2.999, P<0.01), disease duration ( Z=2.141, P<0.05) and treatment duration of GC ( Z=2.460, P<0.05) were higher in group with GIOP than that in group without GIOP, while erythrocyte sedimentation rate (ESR)( Z=2.262, P<0.05), C-reactive protein levels (CRP) ( Z=2.551, P<0.05) and body mass index (BMI) ( t=2.425, P<0.05) were lower and the composition ratio of X-ray staging was worse ( χ2=12.484, P<0.01).⑤ Logistic regression analysis (LR Backward) showed that female gender [ OR(95% CI)=14.240(3.878, 52.288), P<0.01], age [ OR(95% CI)=1.079(1.042, 1.118), P<0.01] and sarcopenia [ OR(95% CI)=2.470(1.192, 5.120), P<0.05] were the risk factors for GIOP in RA patients. Conclusion:The proportion of treatment with GC in RA patients is very high (about 60%), and the prevalence of GIOP is 40.9%, which is closely related to sarcopenia and vitamin D deficiency.

Effect of Wuzi Yanzong Wan on Sperm Apoptosis by Intervening with Mitochondrial Permeability Transition Pore / 中国实验方剂学杂志

Objective:To study the effect of Wuzi Yanzong Wan on the expressions of voltage-dependent anion channel 1 （VDAC1）， adenine nucleotide transposase （ANT）， cyclophilin D （CypD） and other proteins， and analyze its mechanism in intervening with sperm mitochondrial permeability transition pore （mPTP） opening. Method:Forty rats were randomly divided into 4 groups， namely normal group， model group， positive group （Shengjing capsule， 1.6 g·kg-1·d-1）， and Wuzi Yanzong Wan group （4.0 g·kg-1·d-1）， with 10 rats in each group. Except for the normal group， tripterygium wilfordii glycosides （GTW， 30 mg·kg-1） was intragastrically administered for 8 weeks to establish the oligozoospermia model. After the 4th week， each group was given drugs through intragastric administration for 4 weeks， and fasted for 12 h after the last administration. These rats were anesthetized with 3% chloral hydrate， and their testis and epididymis tissues were collected. Western blot was used to determine the protein expressions of VDAC1，ANT，CypD，B-cell lymphoma/leukemia2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3， Caspase-9 in rat testis， Testicular tissue and its ultrastructure were observed under electron microscopy. The apoptosis in spermatogenic cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling （TUNEL）. Result:Western blot results showed that compared with the normal group， the expressions of VDAC1， CypD， Caspase-3， Caspase-9 and Bax/Bcl-2 in the model group were increased （P<0.01）. The expressions of VDAC1， CypD， Caspase-3， Caspase-9 and Bax/Bcl-2 were significantly decreased in the positive group and the Wuzi Yanzong Wan group compared with the model group （P<0.01）. There was no significant change in the expressions of ANT and Bcl-2 protein between the groups. Testicular ultrastructural evaluation showed different sizes and disordered arrangement of sperm mitochondria and a large number of swelling and vacuoles in the model group， while complete structure and neat arrangement of sperm mitochondria and much less swelling and vacuole in positive group and Wuzi Yanzong Wan group. TUNEL results showed that the apoptosis rate of spermatogenic cells in the model group was significantly higher than that of the normal group （P<0.01）， while the apoptosis rate in the positive drug and Wuzi Yanzong Wan group was significantly lower than that of the model group （P<0.01）. Conclusion:Wuzi Yanzong Wan may resist germ cell apoptosis by inhibiting the expressions of VDAC1， CypD and Bax， reducing the permeability of mPTP， and preventing the cascade activation reaction of the Caspase family of apoptosis proteins.

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA.@*METHODS@#COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA.@*RESULTS@#Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ± 16.12]% vs. [17.92 ± 4.91]%, P = 0.02) and serum IL-17 (17.96 ± 9.59 pg/mL vs. 8.05 ± 4.44 pg/mL, P = 0.02), but blood ([5.18 ± 1.09]% vs. [4.15 ± 0.87]%, P = 0.28) and lung levels of Th17 cells ([1.98 ± 0.83]% vs. [2.03 ± 0.98]%, P = 0.91), lung levels of RORγt ([9.58 ± 6.93]% vs. [9.63 ± 5.98]%, P = 0.49) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 68.70 ± 15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ± 1.09]% vs. [9.21 ± 3.56]%, P = 0.01) and lung Th17 cells ([1.98 ± 0.83]% vs. [6.29 ± 1.11]%, P = 0.01) and serum IL-23 (51.55 ± 27.82 pg/mL vs. 154.90 ± 64.60 pg/mL, P = 0.01) and IL-17 (17.96 ± 9.59 pg/mL vs. 39.81 ± 22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ± 16.12]% vs. [29.86 ± 15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ± 6.93]% vs. [15.10 ± 2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ± 944,480.43 vs. 892,958.10 ± 686,808.80, t = 2.32, P = 0.02).@*CONCLUSION@#These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.

Application of Shear Wave Elastography in Type 2 Diabetic Sural Neuropathy / 中国康复理论与实践

Objective:To explore the value of shear wave elastography (SWE) for diagnosis of sural neuropathy in patients with type 2 diabetes mellitus (T2DM). Methods:From September to December, 2017, 119 patients with T2DM were divided into diabetic peripheral neuropathy (DPN) group (n = 61) and non-DPN group (n = 58) according to the diagnosic criteria. In the same period, other 60 healthy volunteers were also recruited as normal group. They were measured the thickness, width, circumference and cross-sectional area of sural nerve, as well as the Young's modulus and shear wave velocity (SWV) with SWE. Based on the results of electrophysiology, the receiver operating characteristic (ROC) curve was drawn to determine the cut-off of the Young's modulus and SWV to differentiate DPN from non-DPN, and their area under the curve was compared. Results:The thickness of sural nerve was more in DPN group than in the normal group (P < 0.05). There were significant differences among all the groups in width, cross-sectional area, circumference, Young's modulus and SWV of sural nerves (P < 0.05). For SWE image, it was yellow-green for DPN group, dark blue for non-DPN group, and uniform light blue for the normal group. The cut-off was 51.65 kPa for Young's modulus, with the area under the curve of 0.925, sensitivity of 86.9% and specificity of 89.7%; while it was 4.15 m/s for SWV, with the area under curve of 0.923, specificity of 89.7% and sensitivity of 85.2%. The diagnostic efficiency for DPN was similar between Young's modulus and SWV (Z = 0.556, P = 0.579). Conclusion:SWE can provide useful information for clinical diagnosis of sural neuropathy after T2DM.

Comparative Study of Transrectal Real-time Tissue Elastography and Magnetic Resonance Diffusion-Weighted Imaging in the Diagnosis and Guided Biopsy of Prostate Cancer / 中山大学学报(医学科学版)

@#【Objectives】 To comparatively analyze the diagnostic performance of transrectal real- time elastography（TRTE）and magnetic resonance diffusion- weighted imaging （DWI）in differentiating benign from malignant prostatic lesions，to evaluate the value of the two methods in guided prostate biopsy，and to investigate the correlation between the two methods and Gleason scores. 【Methods】 A total of 126 patients with suspected prostate cancer underwent prostate biopsy. Preoperative tests of TRTE and DWI were performed in all of the included patients. Combined with pathological results，the diagnostic efficacy of TRTE and DWI for prostate cancer and the effects of prostate biopsy guided by the two methods were compared ，and the relationship between the elastography score and ADC value and Gleason scores were also evaluated.【Results】 The sensitivity，specificity，accuracy of diagnosing prostate cancer by TRTE were 78.8% ，78.3% ，78.6% ，the sensitivity，specificity，accuracy of diagnosing prostate cancer by DWI were 87.9% ，90% ，88.9% ， there was no significant difference of sensitivity and specificity between the two groups（P > 0.05），and the accuracy was statistically different（P < 0.05）. The AUC of elastography score and ADC value were 0.859 and 0.906，the accuracy of the diagnosis of benign and malignant prostate lesions by ADC value method was higher than elastography score ，but there was no statistically significant difference （P > 0.05）. A significant positive correlation was found between elastography score and Gleason scores，while a significant negative correlation was found between ADC value and Gleason scores.【Conclusions】TRTE and DWI is valuable in diagnosis of prostatic lesions. Biopsy guided by the two methods can improve the detection rate of prostate cancer and can provide indicative evidence for tumor differentiation analysis.

Analysis of factors influencing X-ray images of spinal injury in patients with ankylosing spondylitis / 中华风湿病学杂志

Objective@#To investigate factors affecting X-ray structure of the spine in patients with ankylosing spondylitis (AS).@*Methods@#A total of 206 AS patients were recruited. Clinical and laboratory parameters in AS patients were recorded in detail. Disease activity index [Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp)], X-ray structural damage index-modified stoke ankylosing spondylitis spine score (mSASSS) and grading results of radiographic examination of sacroiliac joint were calculated. Statistical analysis using Statistical Package form Soci-science(SPSS) 17.0 Chi-square test, rank test, Logistics regression analysis and other statistical methods were used. Differences of mSASSS levels, spine involvement (mSASSS>0) and rates of bone bridge formation were compared between different groups.@*Results@#Incidences of spine involvement (100%) and bone bridge formation(65.2%) in AS patients ≥40 years old were significantly higher than those in AS patients <40 years old (90.6%、31.9%)(χ2=4.651, P=0.031; χ2=16.647, P<0.01), and the level of mSASSS was also higher (Z=5.575, P<0.01). In AS patients with BMI ≥24 kg/m2, disease duration ≥5 years (49.2%, 50.4%), rates of bone bridge formation was significantly higher than those in AS with BMI <24 kg/m2, but the disease duration (34.5%, 19.7%)(χ2=4.014, P=0.045; χ2=18.173, P=0.03), and mSASSS values were significantly higher (Z=2.281, P=0.023, Z=4.828, P<0.01). Bone bridge formation rate in smoking patients (50.6%) was significantly higher than that in non-smoking patients (31.0%) (χ2=7.346, P=0.007) and mSASSS value was significantly higher (Z=2.045, P=0.041). Bone bridge formation rates in AS with high-ESR and high-CRP(48.6%, 49.0%) were significantly higher than those in patients with normal-ESR and normal-CRP(25.6%, 28.9%)(χ2=10.784, P=0.001; χ2=8.102, P=0.004) and mSASSS value was clearly higher(Z=2.379, P<0.01; Z=3.112, P<0.01). Bone bridge formation rate in AS with BASDAI≥4 or ASDAScrp≥2.1 groups (52.8%, 46.4%) were significantly higher than that in AS with BASDAI<4 or ASDAScrp<2.1 groups (34.2%, 30.7%) (χ2=5.681, P=0.017; χ2=4.646, P=0.031) and mSASSS values were significantly higher (Z=3.887, P<0.01; Z=3.895, P=0.004). Rates of bone bridge formation among different X-ray grading of sacroiliac joint (10.8%, 35.6%, 60.3%) and MRI findings (33.3%, 50.0%, 15.4%) differed with each other (χ2=25.714, P<0.01; χ2=6.855, P=0.032). Logistics regression analysis showed that BMI [OR(95%CI)=1.145(1.037, 1.265), P<0.01], disease duration [OR(95%CI)=1.144(1.055, 1.239), P<0.01], smoking [OR(95%CI)=2.832(1.343, 5.969), P<0.01] and sacroiliac joint X-ray staging [OR(95%CI)=2.584(1.337, 4.997), P<0.01] were risk factors for the bone bridge formation in spine of AS.@*Conclusion@#Spinal involvement in AS is related to disease activity. Bone bridge formation correlateswith disease duration, BMI and disease-status, especially with smoking.

Interpretation of American Gastroenterological Association Clinical Practice update: management of pancreatic necrosis in acute pancreatitis patients / 中国实用外科杂志

American Gastroenterological Association(AGA)has published the latest clinical practice update in Gastroenterology in August 2019. The purpose of this AGA clinical practice update is to review the available evidence and expert recommendations regarding the clinical care of patients with pancreatic necrosis and to offer concise best practice advice for the optimal management of patients with this highly morbid condition. In recent decades,with the improvement in clinical practice,the management of pancreatic necrosis in patients with acute pancreatitis(AP)has undergone great changes. The well-defined step-up approach has been more advocated rather than the traditional open surgery. The treatment of pancreatic necrosis mainly includes two aspects,conservative methods, which consist of antimicrobial therapy as well as nutrition support,and invasive interventions.Drainage and/or debridement of pancreatic necrosis is best indicated in patients with infected necrosis or patients with sterile pancreatic necrosis and persistent clinical symptoms,which need proactive management. A step-up approach consists of percutaneous drainage or endoscopic transmural drainage, followed by direct endoscopic/percutaneous minimally invasive necrosectomy, and then surgical debridement is reasonable. As for the comparison between percutaneous surgical or endoscopic step-up approach,no studies have shown that there are differences between the two in the main clinical outcomes,for instance,mortality. Hence,the choice of specific treatment strategy in different AP centers depends mainly on their available clinical expertise and medical resources.

Imaging features, when and how to perform minimally invasive intervention in infected pancreatic necrosis patients / 中国实用外科杂志

Recently,with the further understanding of infected pancreatic necrosis(IPN),pancreatologists have reached consensuses on that the presence of gas on CT imaging could be the golden standard diagnosis for IPN,the intervention timing for IPN should be delayed to four weeks later,and the step-up approach acts as the first standard treatment strategy for IPN.Whereas in clinical practice,there are substantial new challenges awaiting our solutions,for instance,the lack of accurate and specific diagnostic criteria for IPN without typical gas sign on CT imaging,whether the intervention of wall-off necrosis(WON)which got infected prematurely should be delayed to four weeks later?What's more,whether the endoscopy centered step-up approach is superior to the surgical step-up approach?Is it time to abandon open surgery in IPN management?If not,when should we switch to open necrosectomy?All of these questions are still full of controversies.

Effect of different surface zirconium oxide treatments on binding strength between zirconia and veneering ceramics / 中南大学学报(医学版)

To compare the effect of three different surface zirconium oxide treatments on binding strength and fracture patterns between zirconia and veneering ceramics.
 Methods: A total of 40 zirconia specimens and 10 nickel-chromium alloy were divided into 5 groups (n=10 in each group): a treatment group by zirconium oxide sand-blaste (Group A), a zirconia bonded porcelain group (Group B), a hot-etching solution group (Group C), a non-treatment zirconia (Group D) and a non-treatment nickel-chromium alloy group (Group E). After all treatments, a veneering porcelain (4 mm×4 mm×2 mm) was formed onto the center of all substrate specimens by plastic coating method. Shear bond strength (SBS) test with a universal testing machine was used in each group. Scanning electron microscopy was used to observe the surface morphology of the damaged specimen interface, which was randomly selected from each group.
 Results: The SBS test showed that there was no significant difference in SBS results between the Group A, the Group B and the Group D (both P>0.05), and both of them were significant less than that in the group E (both P<0.05). The SBS results in the Group C were significantly higher than that in the Group D, the Group A, and the Group B (all P<0.05), but there were no significant difference compared with that in the Group E (P<0.05). 
 Conclusion: Sand-blaste and liner application on zirconia ceramic contribute no effect to binding strength between zirconia and veneering ceramics, but hot-etching solution can increase the binding strength between zirconia and veneering ceramics.

Prevalence and reference value of spondyloarthritis features in patients with spondyloarthritis / 中华风湿病学杂志

Objective To explore the prevalence and reference value of disease features of patients with spondyloarthritis. Methods Spondyioarthritis features and laboratory indexes and radiographic indexes of 505 patients with spondyloarthritis (SpA) including 353 patients with ankylosing spondylitis (AS), 62 patients with non-radiographic axial spondyloarthritis (nr-axSpA) and 90 patients with peripheral spondyloarthritis (pSpA) were recorded. One-way analysis of variance, Kruskal-Wallis test, x2-test, Logistic regression were used for statistical analysis. Results Sex ratio ( x2=20.673, P<0.01), age ( x2=22.258, P<0.01), disease duration ( x2=76.052, P<0.01) were different among AS, nr-axSpA and pSpA. Besides, Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp), erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP) and Bath ankylosing spondylitis functional index (BASFI)were different among SpA subgroups ( x2/F=13.196-40.028, P<0.01). Prevalence of inflammatory back pain, peripheral arthritis, preceding infection, positive human lymphocyte antigen (HLA)-B27 and elevated CRP were different among SpA subgroups ( x2=11.416, 32.657, P<0.01). Prevalence of dactylitis in SpA with positive HLA-B27 was lower than that in SpA with negative HLA-B27 ( x2=5.414, P=0.02). Prevalence of enthesitis and dactylitis in SpA patients with peripheral arthritis was higher than that in SpA without peripheral arthritis involvement ( x2=7.177, 14.428, P<0.01). Prevalence of good response to Non-steroid anti-inflammatory drugs. (NSAIDs) in patients with anterior uveitis involvement was higher than SpA without anterior uveitis involvement ( x2=4.578, P=0.032). SpA patients were stratified by total number of SpA features into 4 subgroups (n≤1, n=2, n=3, n≥4). Prevalence of inflammatory back pain, positive HLA-B27, good response to NSAIDs were the top three in all subgroups. Inflammatory back pain and HLA-B27 (+) were risk factors for axSpA (OR=3.254, 3.323, P<0.01). Peripheral arthritis, dactylitis, and preceding infection were risk factors for pSpA (OR=3.759, 4.134, 17.044, P<0.01). Conclusion Inflammatory back pain, HLA-B27 (+) and good response to NSAIDs should be emphasized for the diagnosis of SpA. Inflammatory back pain and HLA-B27(+) always means axSpA. Peripheral arthritis, dactylitis and preceding infection always indicates pSpA.

16S rDNA-based molecular profiles of circulating bacteria in patients with severe acute pancreatitis / 肠外与肠内营养

Objective:This study aims to characterize the bacterial profile presenting in peripheral blood of severe acute pancreatitis (SAP) patients and investigate the potential role of circulating microorganisms in the development of systemic infection.Methods:A total of 30 patients with SAP were recruited in this study and divided into three groups:infected,sepsis and Septic shock (n =10 for each group).The peripheral blood was collected sterilely for extraction of DNA,which was subsequently amplified using the universe primers targeted the V6-V8 region of 16S ribosomal RNA genes.The amplicons were separated by denaturing gradient gel electrophoresis (DGGE),and then the gels were stained and photographed.The bands were cut out and sequenced to determine the closest bacterial relatives.Results:As shown in DGGE profile,multiple DNA bands (3 to 8 bands) were detected in peripheral blood from all (100％) of SAP patients complicated with septic shock.The microorganisms most frequently presenting in the blood of these cases included Escherichia coli,Bacillus coagulans,Pseudomonas putida,Pseudomonas aeruginosa,and Klebsiella pneumonia,with an incidence of 40 ％ or higher.In patients with sepsis,bacterial DNA consisting of 2 to 4 bands was observed in 90％ of the blood samples.The most common bacterial species was Pseudomonas putida (60％),followed by Shigella flexneri (40％),Staphylococcus aureus (30％) and Enterococcusfaecium (20％).By contrast,the positive rate of blood bacterial DNA was relatively lower in infected patients (70 ％).Of them,single bacterial species was commonly found in the blood samples.Conclusions:Our data showed that the bacterial profiles presenting in peripheral blood are distinct among SAP patients with different manifestations.Polymicrobial translocation could contribute to the development of systemic infection,offering novel insights into the pathogenesis of sepsis in SAE The findings are helpful for the prevention and treatment for bacterial infection and complications of SAP.

Clinical study of serum vitamin D binding protein in patients with rheumatoid arthritis associated with secondary osteoporosis / 中华风湿病学杂志

Objective To explore the changes of serum vitamin D binding protein (VDBP) levels in patients with rheumatoid arthritis (RA) and the clinical significance of association between serum VDBP with secondary osteoporosis (OP) in RA.Methods One hundred and sixty patients with RA were enrolled in the study.Eighty-three normal subjects were recruited as the control group.The concentration of serum VDBP was determined by enzyme-linked immuno sorbent assay (ELISA),and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.Clinical and laboratory indexes of RA patients were recorded in detail and disease activity (DAS28) score,health assessment questionnaire (HAQ) and Sharp score according to X-ray examination of both hands were calculated simultaneously.The t test was used to compare the metrological data between the two groups,and the x2 test was used to compare the intergroup rate.The correlation analysis was tested by Pearson correlation analysis,the ROC curve was used to analyze the threshold of the serum VDBP,and the multivariate logistic regression analysis was used for multivariate analysis.Results ① Serum levels of VDBP in RA patients were higher than that in control group [(414±12) ng/ml vs (79±12) ng/ml,t=20.082,P＜0.01].Positive rate of serum levels of VDBP was 67.0％(118/176) in RA patients,which was higher than that in the control group (4.8％)(x2 =87.651,P＜0.01).② The threshold of serum VDBP levels for diagnosing RA was 193.74 ng/ml (AUC=0.943,Youden index=0.796,P＜0.01).③ DAS28 sore in group with positive VDBP was significantly higher than that in group with negative VDBP (P9=0.025).There was significant difference regarding on the incidence of OP in female RA patients between groups with positive and negative VDBP [41.9％(54/129) vs 31.8％(14/44),x2=4.325,P=0.038].④ Linear correlation analysis found that DAS28in RA patients was positively correlated with serum VDBP levels (r=0.252,P=0.019).And anti-CCP was negatively correlated with serum VDBP levels (r=-0.150,P=0.049).⑤ Results of logistic regression analysis showed that sex [OR=9.841,95％CI (1.349,71.810),P=0.024],age [OR=1.154,95 ％CI (1.069,1.245),P＜0.01] and Sharp score [OR=1.102,95％CI (1.002,1.021),P=0.018] were risk factors for OP in RA patients.Conclusion Serum VDBP levels are significantly higher in patients with RA.Meanwhile,serum VDBP levels are correlated with disease activity and secondary OP in RA.

Clinical study of serum fibroblast growth factor 23 levels in patients with rheumatoid arthritis and their association with osteoporosis / 中华风湿病学杂志

Objective To explore the serum levels of fibroblast growth factor 23 (FGF23) in patients with rheumatoid arthritis (RA) and to investigate the relationship between FGF23 and RA disease activity and the occurrence of osteoporosis (OP).Methods Serum levels of FGF23 from 174 cases of patients with RA and 88 normal subjects were detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.All the clinical and laboratory indexes of RA patients were recorded in details,disease activity score (DAS28) and health assess questionnaire (HAQ) were also calculated in the meantime.Radiographic changes in both hands of RA patients were assessed by Sharp's method.T test,nonparametric test,x2 test,correlation analysis and Logistic regressive analysis were used for statistical analysis.Results Serum levels of FGF3 [145.46(67.67,245.93) pg/ml] in RA patients were higher than the control group [32.64(12.34,44.70) pg/ml,Z=11.416,P＜0.01].The positive rate of serum levels of FGF23 (≥71.95 pg/ml) in RA was 74.7％(130/174),while the positive rate in control was 4.5％(4/88,x2=115.16,P＜0.01).The threshold of FGF23 serum levels for diagnosing RA was 48.56 pg/ml (AUC=0.932,Youden index=0.743,P＜0.01,sensitivity 89.1％,specificity 85.2％).In RA patients with serum FGF23 ≥48.56 pg/ml,compared with negative FGF23 group,VAS,HAQ,number of joint swelling and BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were significantly higher in FGF23 positive group (P＜0.05).Linear correlation analysis found that in RA patients with serum FGF23 ≥48.56 pg/ml,anti-CCP was negatively correlated with serum FGF23 levels (r=-0.171,P=0.035).And DAS28 was positively correlated with serum FGF23 (r=0.163,P=0.045).BMD at femoral neck,Ward,GT,Total hip,L4 and L1-4 were negatively correlated with serum FGF23 (P＜0.05).Results of logistic regression analysis showed that sex (OR=8.518,95％CI (2.636,27.522),P＜0.01,age [OR=1.129,95％CI (1.079,1.180),P＜0.01] and Sharp score [OR=1.008,95％CI(1.003,1.013),P=0.001]were risk factors for OP in RA patients.BMI[OR=0.801,95％CI(0.707,0.909),P=0.001] was a protective factor for OP in RA patients.Conclusion Serum FGF23 level is significantly higher in RA patients.Meanwhile,the serum FGF23 level correlates with RA disease activity and BMD.

Clinical study on the serum peroxisome proliferater-activated receptor γlevels in patients with rheumatoid arthritis associated with osteoporosis / 中华风湿病学杂志

Objective To investigate the value of serum levels of peroxisome proliferater-activated receptor (PPAR)γin patients with rheumatoid arthritis (RA) and to explore the associations between serum PPARγwith disease activity of RA and RA-associated osteoporosis (OP).Methods One hundred and one cases of hospitalized patients with RA were enrolled.A total of 88 normal subjects during the same period were recruited as the control group.Levels of serum PPARγwere detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absortiometry.All the clinical and laboratory indexes of RA patients were recorded in detail.T-test (or t'-test) was used for comparison of measurement data between the two groups,non-parametric test was applied for skewed distribution data.Comparison of incidence was analyzed with x2 test,correlation analysis was represented ascorrelation coefficient (r).Results Binary logistic regression analysis was used for multivariate regression analysis.Serum levels of PPARγ(3.38/4.00 ng/ml) in RA patients were higher than thosein normal subjects (2.63/1.76) ng/ml (Z=3.204,P=0.001).The positive rate of serum levels of PPARγin RA was 35.6％ (36/101),while the positive rate in the controls was (2.3％,2/88,x2=32.602,P＜0.01).The incidence of OP in RA was 34.7％(35/101;while the levels of serum PPARγ in RA without OP at femur area (femoral neck,total hip) and lumbar spine (L1,L1-4) were higher than that in RA with OP (P＜0.05).Serum levels of PPARγ between groups with different disease activity had no significant difference (P＞0.05).Serum levels of PPARγ in RA with negative RF or negative anti-CCP were higher than thosetin the RA group with positive RF or positive anti-CCP(P＜0.05).Serum levels of PPARγ in RA were negatively correlated with serum RF,anti-CCP,hemoglobin (P ＜0.05-0.001),and positively correlated with erythrocyte sedimentation rate,platelet,BMD at sites of femur neck andWard (P＜0.05-0.001).Results of binary logistic regression analysis showed that levels of serum PPARγwere protective factors in RA for OP at femurneck [OR=0.577,P=0.005,95％CI (0.394-0.846)],and total hip [OR=0.754,P=0.033,95％CI (0.581-0.978)].Condusion Serum levels of PPARγ in patients with RA are significantly increased,and negatively correlate with autoantibodies.Serum levels of PPARγare protective factors for OP in RA.