Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Efficacy analysis of endoscopic submucosal dissection and transanal endoscopic microsurgery in the treatment of rectal neuroendocrine tumors / 中华消化杂志

Objective:To compare the short- and long-term efficacy and safety of endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) in the treatment of rectal neuroendocrine tumor (NET) with maximum diameter ≤20 mm.Methods:From January 1, 2014 to June 30, 2022, the clinical data of 111 patients with rectal NET with maximum diameter ≤20 mm treated by ESD or TEM at Peking University People′s Hospital were retrospectively analyzed. According to the treatment of ESD or TEM, 111 patients with rectal NET were divided into ESD group (76 cases) and TEM group (35 cases). The clinicopathological characteristics (age, distance from anal margin, depth of invasion, etc.) were compared between patients with tumor maximum diameter<10 mm and 10 to 20 mm, and between ESD group patients and TEM group patients. The clinical efficacy and prognosis were also compared between ESD group and TEM group. The follow-up time was 41 months (16 months, 76 months). The propensity score matching (PSM) method was used to balance the differences of clinical characteristics between ESD and TEM groups. Independent sample t test, Wilcoxon rank-sum and chi-square test were used for statistical analysis. The risk factors of lymph node or distant metastasis were analyzed by univariate and multivariate binary logistic regression. Results:The maximum tumor diameter of 111 patients with rectal NET was (6.6±0.3) mm (ranged from 2 to 20 mm). The maximum tumor diameter of 85 cases (76.6%) was <10 mm and that of 26 cases (23.4%) was between 10 mm and 20 mm. There were statistically significant differences in age, distance from the anal margin and incidence of submucosal infiltration between patients with tumor maximum diameter<10 mm and patients with tumor maximum diameter 10 to 20 mm ((49.8±11.6 ) years old vs. (56.8±13.8) years old; 5.0 cm (4.0 cm, 8.0 cm) vs. 8.0 cm (5.0 cm, 8.0 cm); 69.4%, 59/85 vs. 96.2%, 25/26; t=2.58, Z=-2.23, χ2=6.35, P=0.011, 0.026 and 0.012). The en block resection rate of rectal NET treated with ESD or TEM was 100.0%(111/111), the complete resection rate was 93.7% (104/111), and the postoperative bleeding rate was 2.7% (3/111). There were no postoperative perforation or other major complications. During the follow-up period, there was no local recurrence. The metachronous recurrent rate was 0.9% (1/111), 3.6% (4/111) patients had lymph node or distant metastasis, and there was no death. Compared with patients with tumor maximum diameter<10 mm, more patients with tumor maximum diameter of 10 to 20 mm selected TEM (57.7%, 15/26 vs. 23.5%, 20/85), and the difference was statistically significant ( χ2=10.76, P=0.001). Before PSM, a total of 7 patients in the ESD group had positive vertical margins, and during the follow-up of 21 months (15 months, 48 months), 2 patients had lymph node or distant metastasis and received surgery. The proportion of patients with tumor maximum diameter of 10 to 20 mm and submucosal invasion in TEM group were both higher than those in ESD group (42.9%, 15/35 vs. 14.5%, 11/76; 88.6%, 31/35 vs. 69.7%, 53/76), and the differences were statistically significant( χ2=10.76 and 3.65, P=0.001 and 0.032). After PSM, there were no statistically significant differences in the complete resection rate, postoperative bleeding rate, metachronous recurrence rate, lymph node or distant metastasis rate between ESD group and TEM group (89.3%, 25/28 vs.100.0%, 28/28; 3.6%, 1/28 vs. 0, 0/28; 3.6%, 1/28 vs. 0, 0/28; 0, 0/28 vs.3.6%, 1/28; all P>0.05). However, the operation time and hospital stay of the ESD group were both shorter than those of the TEM group (27.0 min (25.0 min, 30.0 min) vs. 39.0 min (32.0 min, 45.0 min); 5.0 d (4.0 d, 5.0 d) vs. 6.0 d (3.0 d, 9.0 d)), and the differences were statistically significant ( Z=-3.38 and -2.23, P=0.001 and 0.021). Conclusion:The efficacy of ESD and TEM in rectal NET with maximum diameter ≤ 20 mm is equal, however, ESD has the advantage of shorter procedure time and hospital stay.

Normothermic machine perfusion of kidney and ischemia-free kidney transplantation / 器官移植

To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.

Bronchial arteriography CT combined with bronchoscopy in diagnosis of Dieulafoy′s disease (a report of 5 cases) / 中国医师杂志

Objective:To investigate the diagnostic value of bronchial arteriography CT (BA-ACT) combined with bronchoscopy (BS) in bronchial Dieulafoy′s disease (BDD), and the role of bronchial artery embolization (BAE) in the treatment of BDD.Methods:Retrospective analysis was made on the clinical data of 5 patients suspected of being BDD treated by BS in Guangzhou First People′s Hospital or Guangzhou Thoracic Hospital from January 2008 to January 2018 due to hemoptysis. Bronchial arteriography (BAG) and BA-ACT were performed during the operation of interventional embolization. BAG rotary acquisition data were post-processed according to BS findings, and BA-ACT reconstruction images of the diseased bronchi and bronchial arteries were obtained. BS reexamination and clinical follow-up observation were carried out after embolization to analyze the effect of embolization.Results:There were one BDD lesion for the five patients respectively, and the BAG lacked characteristic manifestations. Bronchoscopy revealed BDD foci to present as papillary (case 1-case 3), nodular (case 4), or lirellate (case 5) subbronchial submucosal protrusion lesions. On the BA-ACT reconstruction plot, the BDD lesions of papillary, nodular and carination manifested correspondingly as a bronchial artery branches locally " pointed arch" shaped (cases 1-case 4) or " bead-like" (case 5) fold and protruding toward the bronchial lumen. The BDD lesions of the cases 1-case 4 retraction and disappearance after one BAE were observed by BS examination, and no hemoptysis recurrence during the follow-up period (54-91 months). The ridge like BDD lesion of the case 5 remained unchanged after BAE, and hemoptysis recurred at 71 months after the first BAE; the uncollapsed foci were supplied by two collateral vessels that confirmed by second BAG and BA-ACT, and no hemoptysis for 71 months followed up after second BAE.Conclusions:BA-ACT combined with BS enables a locative and qualitative diagnosis of BDD, and BAE is a very effective treatment method for BDD.

The protective effect and mechanism of N-acetylcysteine on acute kidney injury by up-regulating Sirtuin3 protein expression in septic mice / 中华急诊医学杂志

Objective:To explore the protective effect and mechanism of the antioxidant N-acetylcysteine (NAC) regulating silent information regulator 3 (Sirt3) on acute kidney injury (AKI) in septic mice.Methods:Male C57BL/6 mice were randomly ( random number) divided into the sham operation group (sham), cecal ligation and perforation group (CLP), CLP + NAC (50 mg/kg) and CLP + NAC (100 mg/kg) groups, with 10 mice in each group. The mice were sacrificed 24 h after CLP, and blood and kidney tissue samples were collected. HE staining was used to evaluate the pathological damage of the kidney tissue of mice in each group. ELISA was used to detect serum creatinine (Scr), urea nitrogen (BUN), kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated apolipoprotein (NGAL) levels. Immunohistochemistry was used to detect the expression of Sirt3 protein in kidney tissue. RT-qPCR was used to detect the level of Sirt3 mRNA. Mitochondrial damage of renal tubular epithelial cells was observed under transmission electron microscope, and the mitochondrial density was calculated. Meanwhile, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) in the renal cortex were also detected. Results:Compared with the sham group, in the CLP group, the pathological damage of renal tissue was significantly aggravated ( P<0.001), and the levels of renal function indicators (Scr, BUN, KIM-1 and NGAL) were all increased significantly (all P<0.001). The protein and mRNA expression of Sirt3 were all significantly decreased (all P<0.001), the mitochondrial structure damage of renal tubular epithelial cells was increased, and the mitochondrial density was significantly decreased ( P<0.001). The levels of antioxidant enzymes (SOD, GSH-Px and CAT) in the renal cortex were all significantly decreased (all P<0.001), while the lipid peroxide MDA was significantly increased ( P<0.001). Compared with the CLP group, the renal injury score and renal function indexes (Scr, BUN, KIM-1 and NGAL levels) in the 50 mg/kg NAC pretreatment group were decreased, and the levels of SOD, GSH-Px and CAT in renal tissue were increased, but the differences were not significant. However, pretreatment with 100 mg/kg NAC significantly reduced the pathological damage of kidney tissue caused by CLP ( P<0.001), and significantly decreased the levels of Scr, BUN, KIM-1 and NGAL (all P<0.001). The expression of Sirt3 protein [(50.20±2.79) vs.(20.00±0.75), P<0.001] and mRNA [(0.57±0.07) vs. (0.41±0.07), P<0.001] were all significantly increased. The mitochondrial structure of renal tubular epithelial cells was more stable, and the mitochondrial density was significantly increased [(0.60±0.05) vs. (0.43±0.06), P<0.001]. The levels of SOD [(67.37±3.79) U/mg vs. (21.09±0.89) U/mg, P<0.001], GSH-Px [(265.61±9.61) U/mg vs. (180.00±3.31) U/mg, P<0.001] and CAT [(8.58±0.65) U/mg vs. (5.19±0.58) U/mg, P<0.001] were all significantly increased, while the expression level of MDA was significantly reduced [(40.36 ±1.79) vs. (83.81 ±1.70), P<0.001]. Conclusions:NAC can significantly reduce renal pathological damage, improve renal function, maintain mitochondrial structure stability and reduce oxidative stress levels in septic mice by up-regulating Sirt3 protein expression, and has a significant protective effect on CLP-induced AKI.

Exploration on the experience of long-term external normothermic machine perfusion of discarded human kidney for the first time in China / 中华肾脏病杂志

Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

Clinical experience of different switching schemes of tacrolimus slow-release dosage forms after kidney transplantation: a report of 101 cases / 中华器官移植杂志

Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.

Theoretical Verification of Dynamic Lumbar Interspinous Process Stabilization Device with Memory Alloys / 中国医疗器械杂志

To find an effective method of minimally invasive treatment combining prevention and assistance in the middle zone of conservative treatment and fusion surgery for lumbar degenerative diseases, through the clinical effect observation and the advantage and disadvantage comparison of several commonly used lumbar interspinous dynamic stabilization systems, by analyzing the physiological structure, biomechanics and relevant data of lumbar interspinous processes, based on fully understanding of memory alloy materials, a new dynamic lumbar interspinous fixation device with a memory alloy material has been independently designed and researched, which can not only reconstruct the normal biomechanical characteristics of the lumbar spine and satisfy the normal activities of the human spine, but also avoid damage to the original structure and reduce the incidence of postoperative complications. In addition, the device can be used to optimize the current therapeutic methods. According to our research, the dynamic lumbar interspinous process stabilization device with a memory alloy has theoretically achieved satisfactory results, which can be used to overcome the shortcomings of the existing technology and is superior to the current several dynamic lumbar interspinous process stabilization systems.

Angiographic anatomy of lateral costal artery and its clinical significance / 中国医师杂志

Objective:To study the angiographic anatomy of the lateral costal artery (LCA) and its effect on hemoptysis.Methods:The CT data of angiography and angiographic-CT in 303 patients with hemoptysis in Guangzhou First People′s Hospital were analyzed retrospectively. The origin and travel of the lateral costal artery and the blood supply of the LCA involved in the pulmonary lesion were analyzed.Results:In 303 patients with hemoptysis, 30 LCA were detected in 24 cases, including 12 on the left and 18 on the right, 18 on one side and 6 on both sides. All of them were the first branch of the first segment of the internal thoracic artery (ITA). The level of LCA originating from ITA was located in 1(3.3%) branch above clavicle, 27(90.0%) branches behind clavicle and 2(6.7%) branches below clavicle. LCA entered into the chest behind the first anterior rib, and walked along inner surface of the thorax from the anterior and superior direction to the outer and posterior direction, between the rib-intercostal medial muscle and pleura (i.e., anatomical intrathoracic fascia), and mostly terminated at the axillary midline plane. 28 LCA in 23 patients which can be used for morphological analysis, roughly manifested as follow three shapes: ⑴ 13(46.4%) of them were arc-shaped. The developed LCA was longer and showed shallow or deep arc-shaped curve; ⑵ High flat shape, total 11 LCA (39.3%), the LCA were relatively shorter, position higher and more gentle; ⑶ 4(14.3%) were straight and oblique. The developed LCA was relatively long, and the angle between LCA and ITA was linear. 11 vessels (36.67%) of 10 patients participated in the blood supply of pulmonary lesions, among which 2, 5, 1, 2 and 1 vessels were responsible for the first, second, third, fourth and fifth hemoptysis respectively.Conclusions:The LCA is a relatively common blood vessel and it can be well shown by angiography and angiographic CT. It is of great clinical significance to understand LCA.

Clinical efficacy of lentinan injection combined with recombinant human endostatin in treatment of gastric cancer patients with abdominal cavity metastasis / 肿瘤研究与临床

Objective:To explore the clinical effect of lentinan injection combined with recombinant human endostatin in treatment of gastric cancer patients with abdominal cavity metastasis.Methods:A total of 80 gastric cancer patients with abdominal cavity metastasis were treated in the People's Hospital of Haian City in Jiangsu Province from January 2017 to December 2019 were selected. They were randomly divided into the control group and the observation group according to the number table method, 40 cases in each group. The control group was given FOLFOX (oxalipatin + calcium leucovorin + fluorouracil) chemotherapy combined with recombinant human endostatin, and the observation group was in combination of lentinan injection on the basis of the control group. The short-term efficacy, tumor markers before and after treatment, immune function, angiogenesis related factors levels and adverse reactions of the two groups were analyzed.Results:After treatment, the short-term effective rate in the observation group was higher than that in the control group [67.5% (27/40) vs. 47.5% (19/40), χ2 = 4.256, P < 0.05]. The level of tumor markers like tumor supplied group of factors (TSGF), carcino-embryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) of both groups after treatment was decreased compared with that before treatment; after treatment, the level of TSGF, CEA and CA72-4 in the observation group was lower than that in the control group [TSGF: (48.99±3.14) U/ml vs. (55.17±3.68) U/ml, t = -8.080, P < 0.01; CEA: (0.40±0.09) ng/ml vs. (0.47±0.10) ng/ml, t = -3.291, P = 0.002; CA72-4: (3.51±1.14) U/ml vs. (8.42±2.57) U/ml, t = -11.045, P < 0.01]. The proportion of CD3 +, CD4 +, and the ratio of CD4 +/CD8 + of both groups after treatment was decreased compared with that before treatment. The proportion of CD3 +, CD4 +, and the ratio of CD4 +/CD8 + in the observation group was higher than that in the control group after treatment [CD3 +: (38.53±5.12)% vs. (31.82±4.75)%, t = 6.076, P < 0.01; CD4 +: (25.36±4.39)% vs. (19.12±3.91)%, t = 6.713, P < 0.01; CD4 +/CD8 +: 1.05±0.24 vs. 0.83±0.19, t = 4.546, P < 0.01]. The level of angiogenesis-related factors like p53, vascular endothelial growth factor (VEGF), and transforming growth factor β 1 (TGF-β 1) of the two groups after treatment was decreased compared with that before treatment. The level of p53, VEGF, and TGF-β 1 in the observation group was lower than that in the control group after treatment [p53: (132.86±31.24) ng/L vs. (163.24±33.27) ng/L, t = -4.210, P < 0.01; VEGF: (425.23±36.79) ng/L vs. (673.57±63.28) ng/L, t = -21.458, P < 0.01; TGF-β 1: (35.87±4.03) ng/ml vs. (38.26±4.32) ng/ml, t = -2.559, P = 0.012]. The incidence of grade Ⅲ-Ⅳadverse reactions in the observation group was lower than that in the control group [47.5% (19/40) vs. 62.5% (25/40), χ2 = 6.142, P < 0.05]. Conclusion:Lentinan injection combined with recombinant human endostatin is safe and effective in treatment of gastric cancer patients with abdominal cavity metastasis, and it is worthy of clinical promotion.

A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive

Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P

Safety analysis of endoscopic retrograde cholangiopancreatography and its associated treatments in the elderly / 中华老年医学杂志

Objective:To investigate the safety of endoscopic retrograde cholangiopancreatogra-phy(ERCP)and its associated treatments in the elderly aged 65 years and over, and analyze the related factors leading to postoperative complications.Methods:Totally 512 patients who received ERCP and its associated treatments in the Department of Gastroenterology, Peking University People's Hospital from January 2013 to January 2019 were included retrospectively.The clinical data, operative procedures and postoperative complications were collected.The differences in underlying diseases, operative procedures and postoperative complications between the elderly group(≥65 years old, n=301)and the non-elderly group(n=211)were compared, and the correlations between them were analyzed.Results:The proportion of hypertension, diabetes, heart disease and diverticulum beside the nipple was higher in the elderly group than in the non-elderly group(all P<0.01). The proportion of preoperative medication of anticoagulant and antiplatelet drugs was higher in the elderly group than in the non-elderly group(all P<0.01). There were no significant differences in cholelithiasis, history of biliary surgery, history of ERCP, immunity disease and tumor between the two groups(all P>0.05). Endoscopic sphincterotomy was the most common ERCP-associated treatments in both groups, followed by the order of endoscopic balloon dilation of the nipple, endoscopic biliary stent drainage, pancreatic duct intubation, and pancreatic duct stenting.The proportions of endoscopic papillary balloon dilation and endoscopic biliary stent drainage were 34.6%(104 cases)and 18.9%(57 cases)respectively, in the elderly group, which were statistically significantly higher than 25.6%(54 cases)and 11.4%(24 cases)in the non-elderly group(all P<0.05). The common bile duct diameter and maximum stone diameter were(1.32±0.43)cm and(1.04±0.53)cm, respectively in the elderly group, which were statistically significantly higher than those in the non-elderly group(1.16±0.40)cm and(0.81±0.03)cm respectively, ( t values were -4.23 and -4.76, respectively, all P<0.01). The proportions of endoscopic papillary balloon dilation and biliary stent drainage were statistically significantly higher in elderly patients than in non-elderly patients(all P<0.05). The incidence of intraoperative bleeding was 4.0%(12 cases)and 5.7%(12 cases)in the elderly group and non-elderly group, respectively, with no statistical significance( χ2=0.08, P>0.05). There was no significant difference in the incidence of postoperative pancreatitis, bleeding, perforation, infection and contrast agent-related complications(all P>0.05). Conclusions:Clinically widely used high-risk endoscopic papillary balloon dilation and endoscopic biliary stent drainage(ERCP-associated treatments)are frequently performed in elderly patients, and do not increase intraoperative bleeding and postoperative complications in the elderly.Therefore, ERCP-associated treatments are safe for the elderly.

Tripodalsporormielones A-C, unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems

A chemical investigation on

Preliminary results of multicenter studies on ABO-incompatible kidney transplantation / 中华器官移植杂志

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Retrospective analysis of pediatric kidney transplantation: a report of 244 cases / 中华器官移植杂志

Objective:To explore the clinical characteristics and outcomes of pediatric kidney transplantations at a single center and discuss the related clinical issues.Methods:From January 1990 to October 2019, clinical data were analyzed retrospectively for 244 pediatric renal transplants. The youngest recipient was aged 1.8 years and the median age of pediatric recipients was 12.2 years. The major disease was primary or hereditary glomerulonephritis ( n=160, 69.0%), congenital anomalies of kidney and urinary tract (CAKUT), cystic renopathy and other hereditary nephropathies ( n=55, 23.7%). The donor sources included traditional deceased donor ( n=42, 17.2%), living-related donor ( n=19, 7.8%) and organ donation ( n=183, 75.0%). The median age of donors was 2 years (0-51) and the median weight 12.0(2.7-72.0) kg. From January 2013 to October 2019, 170 cases), the major induction immunosuppression regimen was anti-thymocyte globulin (ATG) ( n=110, 64.7%) or basiliximab ( n=58, 34.1%). The maintenance regimen was tacrolimus + mycophenolic acid (MPA) + glucocorticosteroids. Finally the outcomes and the complications were analyzed. Results:The survival rates of 244 kidney allograft recipients were 98.1%, 94.5% and 93.4% and the graft survival rates 92.6%, 84.2% and 82.0% at 1/3/5 years respectively. Ten recipients died of accident ( n=2, 20.0%), pneumonia after transplantation ( n=2, 20.0%) and intracranial hemorrhage ( n=2, 20.0%). Thirty-three recipients lost their allografts mainly due to intravascular thrombosis in graft ( n=5, 14.3%), acute rejection ( n=5, 14.3%) and death ( n=9, 25.7%). Besides, among 109 deceased donor allograft recipients, the postoperative outcomes were delayed graft function recovery (DGF) ( n=27, 24.8%), arterial thrombosis ( n=6, 5.5%), venous thrombosis ( n=1, 0.9%), graft perirenal hematoma ( n=6, 5.5%), raft artery stenosis ( n=10, 9.2%) and graft ureteral fistula ( n=1, 0.9%). The incidence of acute rejection was 17.5% and 23.2% at 1/3 year respectively. The recurrent rate of primary disease was 6.9%, including primary FSGS ( n=3, 42.9%) and IgA nephropathy ( n=2, 28.6%). At 1/3 year post-operation, the incidence of pulmonary infection was 16.9% and 22.4% and the incidence of urinary tract infection 26.9% and 31.7%. Excluding recipients with graft failure, the estimated glomerular filtration rate (eGFR) at 1/2/3 year postoperatively was (80.3±25.2), (81.4±27.8) and (71.8±27.6) ml/(min·1.73 m 2)respectively. Conclusions:The outcomes of pediatric renal transplantations are excellent at our center. Future efforts shall be devoted to optimizing the strategies of donor kidney selection and strengthening preoperative evaluations, perioperative and postoperative managements for improving the long-term outcomes of pediatric renal transplantations.

Protective effects of Klotho protein on acute kidney injury in septic mice and its mechanism / 中华危重病急救医学

Objective? To? investigate? the? protective? effects? of? Klotho? protein,? a? kind? of? single-pass?transmembrane?protein,?on?acute?kidney?injury?(AKI)?in?septic?mice?and?its?mechanism.? Methods? Sixty?SPF?healthy?male?C57BL/6?mice?(6-8?weeks)?were?randomly?divided?into?sham?operation?group?(Sham?group),?sepsis?model?group?(CLP?group)?and?Klotho?protein?injection?group?(CLP+KL?group),?with?20?in?each?group.?The?septic?AKI?mice?model?was?established?by?cecal?ligation?and?puncture?(CLP);?Sham?group?had?the?same?procedure?except?that?the?cecal?was?not?ligated.?The?CLP+KL?group?was?received?Klotho?protein?(0.02?mg/kg)?by?intraperitoneal?consecutive?injection?for?4?days?after?operation;?Sham?group?and?CLP?group?were?injected?with?the?same?amount?of?saline.?Blood?samples?were?obtained?at?24?hours?after?operation,?the?levels?of?serum?creatinine?(SCr)?and?urea?nitrogen?(BUN)?were?measured?by?sarcosine?oxidase?and?urease?method.?The?mice?were?sacrificed?under?anesthesia?at?5?days?after?operation?to?harvest?renal?tissues,?and?the?pathological?damage?of?the?kidney?was?evaluated?by?hematoxylin-eosin?(HE)?staining.?The?ultrastructure?of?mitochondria?in?mouse?renal?tubular?epithelial?cells?was?observed?under?transmission?electron?microscope.?The?levels?of?reduced? glutathione?hormone?(GSH),?malondialdehyde?(MDA)?and?nitric?oxide?synthase?(NOS)?in?mitochondrion?were?determined?by?micro-enzyme?method,?thiobarbituric?acid?method,?colorimetry?method,?respectively.?The?protein?expressions?of?Klotho,?Bcl-2?and?cytochrome?C?(Cyt?C)?were?detected?by?Western?Blot.? Results? The?pathological?structure?of?the?kidneys?in?the?Sham?group?was?clear?and?intact.?Compared?with?the?Sham?group,?the?renal?tissue?edema?of?the?mice?in?the?CLP?group?was?significant,?and?the?transparent?tube?type?was?observed?in?the?small?lumen,?and?the?interstitial?inflammatory?cells?infiltrated;?the?levels?of?SCr?and?BUN?were?significantly?increased?[SCr?(μmol/L):?182.60±6.97?vs.?47.20±5.37,?BUN?(mmol/L):?53.70±5.12?vs.?18.70±2.62,?both?P?<?0.01];?the?mitochondria?were?swollen?and?deformed,?the?sputum?structure?was?destroyed,?the?matrix?density?was?decreased,?the?outer?membrane?was?lost,?and?the?levels?of?MDA,?GSH?and?NOS?were?significantly?increased?[MDA?(μmol/g):?1.172±0.046?vs.?0.746±0.094,?GSH?(μmol/g):?5.765±0.059?vs.?4.223±0.072,?NOS?(kU/g):?0.91±0.05?vs.?0.68±0.03,?all?P?<?0.01];?the?protein?expressions?of?Klotho?and?Bcl-2??in?renal?tissue?were?decreased,?and?the?protein?expression?of?Cyt?C?was?increased?(Klotho/β-actin:?0.188±0.020?vs.?0.538±0.024,?Bcl-2/β-actin:?0.311±0.010?vs.?0.391±0.015,?Cyt?C/β-actin:?0.226±0.010?vs.?0.135±0.006,?all??P?<?0.01).?Comparing?with?the?CLP?group,?the?glomerular?and?tubular?tissue?epithelial?edema?and?the?small?lumen?in?the?CLP+KL?group?were?reduced;?the?levels?of?SCr?and?BUN?were?significantly?decreased?[SCr?(μmol/L):?85.70±7.23?vs.?182.60±6.97,?BUN?(mmol/L):?35.30±3.50?vs.?53.70±5.12,?both?P?<?0.01];?the?mitochondrial?structure?was?relatively?intact;?the?levels?of?MDA,?GSH?and?NOS?were?significantly?decreased?[MDA?(μmol/g):?0.958±0.072?vs.?1.172±0.046,?GSH?(μmol/g):?4.756±0.107?vs.?5.765±0.059,?NOS?(kU/g):?0.79±0.02?vs.?0.91±0.05,?all?P?<?0.01];?the?protein?expressions?of?Klotho,?Bcl-2?were?significantly?increased,?but?the?protein?expression?of?Cyt?C?was?significantly?decreased?(Klotho/β-actin:?0.336±0.011?vs.?0.188±0.020,?Bcl-2/β-actin:?0.474±0.017?vs.?0.311±0.010,?Cyt?C/β-actin:??0.168±0.006?vs.?0.226±0.010,?all?P?<?0.01).? Conclusion? Klotho?protein?has?significant?protective?effects?on?AKI?in?septic?mice,?and?its?mechanism?is?related?to?maintaining?mitochondrial?structural?integrity?and?oxidative?stress?response.

Clinicaland prognostic features of lipoprotein glomerulopathy in renal allografts / 中华器官移植杂志

Objective@#To explore the clinical and prognostic features of lipoprotein glomerulopathy (LPG) in renal allografts.@*Methods@#Retrospective analysis was performed for two case of LPG in renal allografts. The onset time was 6 and 9 years after living transplantation respectively. Initial symptoms included proteinuria and hypoproteinemia. Color Doppler ultrasound showed an enlarged graft size and greater parenchymal echogenicity. One patient had hyperlipemia and elevated apolipoprotein E (ApoE). Methylprednisolone pulse was offered with an early control of hyperlipidaemia and proteinuria by fenofibrate and angiotensin-converting enzyme inhibitors (ACEIs). Yet it had no effect on graft function. The definite diagnosis was made by graft biopsy. Pathological examination indicated non-homogeneous lipid deposition in glomerular capillary, glomerular sclerosis, mesangial hypercellularity and tubular atrophy.@*Results@#During a follow-up period of 8 and 10 years post-transplantation, two cases eventually lost their grafts within 2 and 1 year after biopsy respectively. With long-term dietary control and drug therapy, regular dialysis continued and both awaited a second transplantation.@*Conclusions@#LPG is generally steroid-resistant and refractory in renal allografts. And routine biopsy is recommended for patients with a high risk of occurrence. Early controls of hyperlipemia and hypoproteinemia and other risk factors should be also properly managed.

Survey on the use of glucocorticoids in severe community-acquired pneumonia in intensive care unit of forty-five hospitals in Zhejiang Province / 中华危重病急救医学

Objective To investigate the use of glucocorticoids in patients with severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) of Hospitals in Zhejiang Province and to provide a reference for guiding clinical use of SCAP patients. Methods To draw up a questionnaire with reference to the Chinese and international guidelines, and to investigate the knowledge of community-acquired pneumonia (CAP) related guidelines and the use of glucocorticoids in patients with SCAP by doctors in hospitals above secondary level in Zhejiang Province by Email. Then the valid questionnaire was analyzed. Results In June 2016, 340 questionnaires were distributed, and all were returned after 2 months, with 333 of valid; 333 doctors from 45 ICUs in Zhejiang Province participated in the survey. ① The knowledge of CAP-related guidelines in ICU doctors: 79.58% (265/333) of the doctors had read the CAP guidelines, and those who work over 10 years had a higher reading rate than those with 1-5 years and 6-10 years [93.07% (94/101) vs. 74.00% (111/150), 73.17% (60/82), both P < 0.05]. Post-graduates and above had higher reading rates than undergraduates [85.35% (134/157) vs. 74.43% (131/176), P < 0.05]. Senior doctors had higher reading rates than the junior and intermediate doctors [93.07% (94/101) vs. 71.43% (80/112), 75.83% (91/120), both P < 0.05]. The rate of understanding the clinical application of glucocorticoids was 13.81% (46/333). The doctors who work over 10 years and the seniorshad a relatively high awareness rate, 23.76% (24/101) and 20.79% (21/101) respectively. However, there was no significant difference in the awareness rate between doctors with different degrees and different levels of hospitals. ② For the use of glucocorticoids in different causes of pneumonia, 44.74% (149/333) of doctors routinely used glucocorticoids in severe viral pneumonia. The proportion of glucocorticoids used in severe bacterial pneumonia, severe fungal pneumonia, severe pneumocystis pneumonia, chronic obstructive pulmonary disease (COPD) and severe pneumonia were 22.82% (76/333), 9.31% (31/333), 22.52% (75/333) and 18.32% (61/333), respectively. ③ The way of glucocorticoid usage: 79.58% (265/333) of doctors chose methylprednisolone, 4.20% (14/333) chose hydrocortisone, 1.20% (4/333) chose dexamethasone, and 15.02% (50/333) had not use glucocorticoids. The proportion of physicians who chose to use glucocorticoids within 24 hours of admission and 1-7 days after admission were 52.65% (149/283) and 47.35% (134/283), respectively. Glucocorticoids were used more in doctors with lower academic qualifications and hospitals within 24 hours. The undergraduate degree was 61.39% (97/158), and the second-grade class hospital was 67.50% (27/40). Among the doctors who chose methylprednisolone, 60.75% (161/265) prescribe the dose ≤80 mg/d;79.15% (224/283) chose the course of ≤7 days. The number of years of work, education, professional title and hospital grade had no significant effect on the choice of methylprednisolone and the course of treatment. Conclusions ICU doctors of 45 hospitals in Zhejiang Province have a high degree of heterogeneity in the understanding of the use and guidelines of glucocorticoids in SCAP. It is necessary to strengthen the ICU doctor's study of clinical guidelines at home and abroad and to develop a glucocorticoid use plan according to the specific conditions of patients, so that SCAP patients can benefit more.

Clinicopathological analysis of invasive micropapillary carcinoma of the breast: 47 cases / 中华内分泌外科杂志

Objective To investigate the clinical pathological characteristics and the prognosis of the invasive micropapillary carcinoma (IMPC) of breast cancer.Methods The clinical pathological characteristics of 47 IMPC patients treated in the Second Hospital of Jilin University from Jan.2010 to Dec.2016 were retrospectively analyzed.A long term survival has been followed.Results 47 IMPC patients were all female.The median age was 56(34-76) years old.The median diameter of the tumor was 1.9(0.8-7.0) cm.The rate of axillary lymph node metastasis was 66.7％ (30/44),the median number of axillary lymph node metastasis was 9.5 (1-55),and the metastasis number of 1 to 3 accounted for 43.3％ (13/30),the metastasis number of 4 to 9 accounted for 6.7％ (2/30),and the metastasis number more than 10 accounted for 50％ (15/30).The lymphatic invasion rate was 40.2％(39/97),and the skin and (or) the nipple invasion rate was 15.6％(7/45).The positive rate of ER,PR,HER2,E-Cadherin was 95.7％(44/46),91.3％(42/46),10.5％(4/38),100％(40/40),respectively.The tumor cell growth index marked by Ki-67 was 1％-80％,and 78.3％ patients' tumor cell growth index marked by Ki-67 were more than 20％.Conclusions IMPC is a relatively rare special type of breast cancer,which typically occurs at middle-aged and old female.The expression of ER,PR,E-Cadherin is high and the expression of HER2 is low.It has strong ability and high positive rate of lymph node metastasis,lymphatic invasion,and poor prognosis.