Predictive value of serum uric acid/albumin ratio for acute kidney injury after cardiac valve surgery / 中华肾脏病杂志

Objective:To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery.Methods:The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators.Results:A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR ( OR=1.467, 95% CI 1.308-1.645, P<0.001), age ( OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation ( OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin ( OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve ( AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825, P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions:For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.

Danggui Buxuetang Inhibits Mitochondrial Fission and Apoptosis of Podocytes in Rat of Diabetic Kidney Disease via AKAP1/Drp1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of Danggui Buxuetang on the mitochondrial fission and apoptosis of podocytes in the rat model of diabetic kidney disease （DKD） and to explore the protective effect and mechanism of Danggui Buxuetang on DKD rats. MethodSD rats were randomized into a modeling group （n=65， fed with a high-sugar and high-fat diet） and a normal group （n=10， fed with a normal diet）. After 6 weeks， the modeled rats were injected intraperitoneally with streptozotocin （STZ） for the modeling of type 2 diabetes mellitus （T2DM）. Sixty T2DM rats were randomized into model， irbesartan （0.014 g·kg-1）， and low-， medium-， and high-dose （0.36， 0.72， 1.44 g·kg-1， respectively） Danggui Buxuetang groups and administrated with corresponding drugs by gavage for 16 weeks. The levels of fasting blood glucose （FBG） and 24 h urinary protein （24 h UTP） were determined at the end of the 16th week. The pathological changes of the renal tissue were observed by hematoxylin-eosin and Masson staining. The mitochondrial ultrastructure of rat podocytes was observed by transmission electron microscopy. The level of reactive oxygen species （ROS） in the renal tissue of rats was measured by the fluorescent probe labeling of dihydroethidium （DHE）. The apoptosis of renal cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL）. The expression levels of Synaptopodin， Podocin， and cleaved caspase-3 in renal podocytes were detected by the immunohistochemical method （IHC）. Western blot was employed to determine the protein levels of A-kinase anchoring protein 1 （AKAP1）， phosphorylated dynamin-related protein 1 （p-Drp1）， mitofusin-2 （Mfn2）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultCompared with the control group， the model group showed elevated levels of FBG and 24 h UTP， mesangial hyperplasia， basement membrane thickening， mitochondrial swelling， mitochondrial crista breakage and disorder， and increased ROS and TUNEL-positive cells. In addition， the model group showcased down-regulated expression of Synaptopodin and Podocin， increased expression of cleaved Caspase-3， up-regulated protein levels of AKAP1 and p-Drp1 ， and down-regulated protein levels of Mfn2 and Bcl-2/Bax （P<0.01）. Compared with the model group， high-dose Danggui Buxuetang lowered the levels of FBG and 24 h UTP， alleviated the pathological injuries of the renal tissue and the mitochondrial injury of podocytes， decreased ROS and TUNEL-positive cells， promoted the expression of Synaptopodin and Podocin， inhibited the expression of cleaved Caspase-3， down-regulated the protein levels of AKAP1 and p-Drp1， and up-regulated the protein levels of Mfn2 and Bcl-2/Bax （P<0.05， P<0.01）. ConclusionDanggui Buxuetang may inhibit mitochondrial fission and apoptosis of podocytes and reduce urine protein by regulating the AKAP1/Drp1 pathway， thereby delaying the progression of DKD.

Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network / 中华儿科杂志

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Disease burden attributable to alcohol consumption in China in1990 and 2019 / 公共卫生与预防医学

Objective To compare and analyze the disease burden caused by drinking in China in 1990 and 2019. Methods The global disease burden database 2019 was used to analyze the attribution score (PAF), mortality, disability adjusted life year (DALY) and other indicators attributed to drinking in China in 1990 and 2019. The disease burden caused by alcohol consumption was compared between China and the world as well as different social demographic index (SDI) regions. Results From 1990 to 2019, the PAF attributed to drinking increased by 12.85%. The number of deaths attributed to drinking increased to 514 700, and the mortality increased to 36.18/100 000, while the DALY attributed to drinking increased to 17.2651 million person-years, and the DALY rate increased by 5.16%. The disease burden attributed to drinking was higher in men than that in women, and the attributable mortality and DALY rate in the elderly over 70 years old were higher than those in the young. From 1990 to 2019, the attributable disease burden of esophageal cancer was the highest in China, followed by colorectal cancer. Compared with the world and different SDI regions, China had the lowest standardized DALY rate attributed to drinking. Conclusion Drinking is one of the important risk factors for related diseases and cancers in China, and effective intervention measures should be taken for key populations.

Treatment of patent ductus arteriosus in very preterm infants in China / 中华儿科杂志

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

Progress on the researches of acupuncture preconditioning before surgery / 中国针灸

This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.

Non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ2=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

Incidence of acute kidney injury following pancreaticoduodenectomy and related risk factors in elderly patients / 中华肾脏病杂志

Objective:To investigate the incidence of acute kidney injury (AKI) following pancreaticoduodenectomy and related risk factors in elderly patients.Methods:The clinical data of elderly patients who underwent pancreaticoduodenectomy in Henan Provincial People′s Hospital from January 2017 to June 2020 were collected retrospectively. According to the changes of serum creatinine within 48 h or 7 days after operation, the patients were divided into AKI group and non-AKI group. The basic clinical characteristics of the two groups were compared, and the incidence of AKI was calculated. Multivariate logistic regression model was used to analyze the risk factors of postoperative AKI.Results:A total of 322 elderly patients were enrolled, with age of (67.1±5.2) years old (60-85 years old) and 186 males (57.76%). Among 322 elderly patients, there were 41 patients (12.73%) suffering from AKI following pancreaticoduodenectomy. Compared with the non-AKI group, the level of bilirubin in AKI group was higher ( Z=-2.012, P=0.044), and the level of hemoglobin in AKI group was lower ( Z=-2.111, P=0.035). Multivariate logistic regression analysis showed that increased preoperative total bilirubin ( OR=1.003, 95% CI 1.000-1.006, P=0.027) and postoperative exploratory laparotomy ( OR=3.936, 95% CI 1.071-14.460, P=0.039) were the independent influencing factors for AKI after pancreaticoduodenectomy in elderly patients. Conclusions:The incidence of AKI after pancreaticoduodenectomy in elderly patients is 12.73%. Preoperative high bilirubin and postoperative exploratory laparotomy may be the independent risk factors for AKI after pancreaticoduodenectomy in elderly patients.

Mechanism of Modified Shengjiangsan in Treatment of IgA Nephropathy Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， targets， and signaling pathways of modified Shengjiangsan in the treatment of immunoglobulin A nephropathy （IgAN） based on network pharmacology， and to explore its underlying mechanism through molecular docking and experimental verification on animals. MethodThe active ingredients and related targets of modified Shengjiangsan were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， UniProt， SwissTargetPrediction， and literature review. IgAN-related targets were obtained from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Cytoscape 3.9.0 was used to construct the regulation network of the related targets of Shengjiangsan and IgAN， and the protein-protein interaction （PPI） network was plotted by STRING. The common genes were analyzed for gene ontology （GO） functional annotation and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment by Metascape. Key targets and main active ingredients were selected for molecular docking by AutoDockTools 1.5.6. The experimental model of IgAN was induced by bovine serum albumin（BSA， ig） combined with lipopolysaccharide （LPS， iv） and the complex of CCl4 and castor oil （sc） in rats. The model rats were treated with modified Shengjiangsan and benazepril hydrochloride for four weeks. The rats were sacrificed after drug administration. The levels of transforming growth factor-β1 （TGF-β1） and interleukin-6 （IL-6） in the serum and kidney tissues were detected by enzyme-linked immunosorbent assay（ELISA）， immunohistochemistry， Real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot. ResultA total of 105 active ingredients were obtained according to oral bioavailability（OB）， drug-likeness（DL）， and literature screening. There were 124 common genes and 59 core targets. Neurotrophic tyrosine receptor kinase 1 （NTRK1）， cullin-3 （CUL3）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， exportin 1 （XPO1）， and other targets might be closely related to IgAN. As predicted by KEGG enrichment analysis， the treatment of IgAN with modified Shengjiangsan mainly involved the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， nuclear transcription factor-kappa B （NF-κB） signaling pathway， and cytokine-cytokine receptor interaction signaling pathway. As revealed by molecular docking， the main active ingredients in modified Shengjiangsan showed stable binding activities with NTRK1， CUL3， TP53， EGFR， and XPO1 in the core targets， indicating that it presumedly regulated inflammatory responses by affecting NTRK1， CUL3， TP53， EGFR， and XPO1 target proteins. The results of experimental verification on animals showed that the expression levels of cytokines TGF-β1 and IL-6 in the serum and kidney tissues of IgAN rats were significantly decreased by modified Shengjiangsan， suggesting that Shengjiangsan might inhibit excessive fibrosis， and inflammatory and immune responses by regulating signaling pathways such as cytokine-cytokine receptor interaction， PI3K/Akt， and NF-κB. ConclusionModified Shengjiangsan may treat IgAN through multiple targets and pathways. Its mechanism may be related to the inhibition of excessive fibrosis， and inflammatory and immune responses by affecting the expression of NTRK1， CUL3， TP53， EGFR， and XPO1 and the regulation of the cytokine-cytokine receptor interaction， PI3K/Akt， NF-κB， and other signaling pathways.

Roles of Pyroptosis and Necroptosis in Diabetic Kidney Disease and Its Regulation with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

The increasing incidence of obesity and diabetes has made diabetic kidney disease （DKD） the main cause of chronic kidney disease and end-stage renal disease. Despite current pharmacological interventions for blood glucose control and renin-angiotensin system inhibition， the risk of kidney disease progression and complications remains high. At present， the pathogenesis of DKD has been clarified to be related to chronic inflammatory response， oxidative stress， glucose and lipid metabolism disorders， and hemodynamic abnormalities. According to recent studies， the programmed cell deaths （PCD） of renal intrinsic cells such as pyroptosis and necroptosis play a key role in the occurrence and development of DKD. Pyroptosis and necroptosis， the two newly discovered routes of PCD， can protect the hosts from being invaded by microbial pathogens， but their dysregulation is associated with multiple autoimmunity and autoinflammatory responses. Pyroptosis and necroptosis are closely interlinked and cross-regulated. Different from apoptosis， these two cellular suicide mechanisms cause membrane rupture and release of cell contents through their respective gasdermin D （GSDMD） and mixed lineage kinase domain-like protein （MLKL）， with damage-associated molecular patterns （DAMPs） and inflammatory cytokines like interleukin-1β （IL-1β） involved to trigger inflammation， and chronic inflammatory responses are key factors leading to the progression of DKD. Traditional Chinese medicine （TCM） has long been employed for the prevention and treatment of DKD and the resulting clinical outcomes are remarkable. TCM has been proved to exert a protective effect against DKD by affecting the expression of nucleotide oligomerization domain-like receptor protein 3 （NLRP3） inflammasome， receptor-interacting protein kinase 3 （RIPK3）， and MLKL. This paper reviewed the relationship of pyroptosis and necroptosis with DKD and its intervention with TCM.

Effect of Modified Shengjiangsan on Gd-IgA1 in IgA Nephropathy Rats： Based on C1GALT1/C1GALT1C1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A （IgA） nephropathy was observed. The microRNA-148b （miRNA-148b）， interleukin 6 （IL-6）， core 1 beta 1，3-galactosyltransferase （C1GALT1）， molecular chaperone Cosmc （core1β3-Gal-T-specific molecular chaperone C1GALT1C1）， and galactose-deficient IgA1 （Gd-IGA1） in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy. MethodA total of 42 SPF male SD rats were randomized into the normal group （8rats） and modeling group （34 rats） with the random number table method. After one week of adaptive feeding， rats for modeling were given bovine serum albumin （BSA， gavage）， lipopolysaccharide （LPS， injection into tail vein）， carbon tetrachloride （CCl4， subcutaneous injection）， and castor oil to induce IgA nephropathy. After modeling， two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group， low-dose Chinese medicine group （modified Shengjiangsan，6.27 g·kg-1）， high-dose Chinese medicine group （modified Shengjiangsan，12.54 g·kg-1）， and benazepril group （10 mg·kg-1） with the random number table method， 8 in each group. The administration （gavage， once a day） lasted 4 weeks. The 24-h urinary total protein （24 h-UTP） was detected at the end of the 1st， 9th， and 13th week of the experiment. At the 14th week， after anesthesia， femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin （ALB）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay （ELISA）. Based on hematoxylin-eosin （HE）/Masson/periodic Schiff-methenamine silver （PASM） staining， the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b， IL-6， C1GALT1， and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of mirNA-148b， IL-6， C1GALT1， and C1GALT1C1， and Western blot was used to detect the protein levels of IL-6， C1GALT1， and C1GALT1C1. ResultCompared with normal group， the model group showed increase in the content of 24 h-UTP， SCr， ALT， IL-6， and GD-IGA1 （P<0.05）， decrease in ALB content （P<0.05）. Moreover， rats in the model group demonstrated hyperplasia of glomerular mesangial cells， thickening of mesangial area， podocyte foot process effacement， and a large number of granular IgA immune complex in the mesangial area. In addition， the model group showed increase in the expression of IL-6 in mesangial area and podocytes， decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes， enhanced expression of IL-6 mRNA and miRNA-148b （P<0.01）， weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA （P<0.01）， rise of IL-6 protein expression （P<0.01）， and reduction in the protein expression of C1GALT1 and C1GALT1C1 （P<0.01）. Compared with the model group， modified Shengjiangsan decreased the content of 24 h-UTP， SCr， ALT， IL-6， and Gd-IGA1 （P<0.05） and increased the content of ALB （P<0.05， P<0.01）. Moreover， with the treatment of this Chinese medicine， the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased， and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover， the expression of IL-6 mRNA and miRNA-148b was decreased （P<0.01）， and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased （P<0.01）. The protein expression of IL-6 was decreased （P<0.05， P<0.01）， and the protein expression of C1GALT1 and C1GALT1C1 was enhanced （P<0.05， P<0.01）. The Chinese medicine group showed obvious dose-effect trend. ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats， restore the expression of C1GALT1 and C1GALT1C1， and decrease the generation of Gd-IGA1， so as to reduce renal pathological damage and proteinuria， protect the kidney protection， and finally delay the disease progression. Moreover， the effect is enhanced with the rise of dose.

Neurovascular coupling analysis of working memory based on electroencephalography and functional near-infrared spectroscopy / 生物医学工程学杂志

Working memory is an important foundation for advanced cognitive function. The paper combines the spatiotemporal advantages of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to explore the neurovascular coupling mechanism of working memory. In the data analysis, the convolution matrix of time series of different trials in EEG data and hemodynamic response function (HRF) and the blood oxygen change matrix of fNIRS are extracted as the coupling characteristics. Then, canonical correlation analysis (CCA) is used to calculate the cross correlation between the two modal features. The results show that CCA algorithm can extract the similar change trend of related components between trials, and fNIRS activation of frontal pole region and dorsolateral prefrontal lobe are correlated with the delta, theta, and alpha rhythms of EEG data. This study reveals the mechanism of neurovascular coupling of working memory, and provides a new method for fusion of EEG data and fNIRS data.

Mesh meta-analysis of the risk of pancreatic fistula after pancreatoduodenectomy by different surgical methods / 中华胰腺病杂志

Objective:To evaluate the impact of laparotomy pancreatoduodenectomy (OPD), laparoscopic pancreatoduodenectomy (LPD) and Da Vinci robot assisted pancreatoduodenectomy (RPD) on the risk of pancreatic fistula in postoperative patients.Methods:The key words were laparoscopic, pancreaticoduodenectomy, robot, DaVinci, Whipple, complication, fistula, pancreaticoduodenectomy, laparoscopy, robot, postoperative complications and pancreatic fistula, and the databases of CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed, EMBASE and web of science were searched until August 1, 2020 for retrospective cohort studies and randomized controlled trials comparing the efficacy of OPD, LPD and RPD. The articles were screened according to the pre-set inclusion and exclusion criteria, and the quality of the articles was evaluated and the data were extracted. Based on Bayesian framework, R4.0.2, Revman 5.3 and Stata 16.0 software were used to analyze the extracted data for mesh meta analysis.Results:Thirty articles involving 3 428 patients were included, including 26 retrospective cohort studies and 4 randomized controlled studies. Mesh meta-analysis showed that in the incidence of pancreatic fistula, there was no significant difference between LPD and OPD, between LPD and RPD ( OR=0.93, 95% CI 0.63-1.4; OR=1.4, 95% CI 0.87-2.2, P<0.05), but the incidence of postoperative pancreatic fistula was significantly lower than that of OPD ( OR=1.5, 95% CI 1.1-2.1, P<0.05), 95% CI 1.12.1; P>0.05). The risk probability of pancreatic fistula was ranked as RPD (0.00), LPD(0.34) and OPD(0.65), that is, for the risk of postoperative pancreatic fistula, the advantages and disadvantages of the three surgical methods were ranked as RPD, LPD and OPD. Conclusions:Compared with OPD, RPD can significantly reduce the risk of pancreatic fistula after PD and improve the quality of operation; there was no significant difference between LPD and RPD in the incidence of postoperative pancreatic fistula, and both of them were safe and feasible.

The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs / 药学学报

Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.

Improvement of Transdermal Delivery of Aciclovir Aliphatic Ester Prodrugs by Using Supersaturated System / 中国药房

OBJECTIVE：To prepare supersaturated system of lip ophilic aci clovir（ACV）prodrug，and to increase the cutaneous bioavailability of ACV. METHODS ：Three prodrugs of ACV were synthesized by anhydride acylation ，i.e. aciclovir acetate （ACV-Ace），butyrate（ACV-But）and hexanoate （ACV-Hex）. The structures of ACV and three ACV prodrugs were confirmed by 1H-NMR and HRESI-MS ；the concentrations of ACV and three ACV prodrugs were determined by UPLC-triple quadrupole tandem mass spectrometry ，and saturated solubility of them in different volume fractions of propylene glycol-water solution was calculated. The compound with the greatest potential of form supersaturated system was screened out. The supersaturated system of that compound was prepared by co-solvent method. The effect of hydroxypropyl methylcellulose E 3 （HPMC E 3） on its physical stability was observed by light microscope. Vertical Franz diffusion cells were used to study the effects of degree of supersaturation （DS）and HPMC E 3 on the deposited amount of drug in the excised porcine skin after using the supersaturated system for 1 h. The distribution of ACV in the excised porcine skin was determined by frozen slicing stratified quantitative method after using the supersaturated system and marketed aciclovir cream for 1 h. RESULTS ：Three ACV prodrugs were successfully synthesized. The established quantification methods met the requirements of biological sample analysis. Among all of the three ACV prodrugs ， ACV-Hex showed the lowest saturated solubility in water [ （0.5±0.0）mmol/L] a nd the highest saturated solubility in propylene glycol [（53.4 ± 14.2）mmol/L]，which made it potentially feasible to form supersaturated system with high DS. In 10％propylene glycol-water system ，the addition of HPMC E 3 163.com enabled ACV-Hex supersaturated systems ，with DS no morethan 4，to maintain physical stability within 1 h. The total deposited amount （ACV + ACV-Hex ） in skin after the application of ACV-Hex supersaturated system with DS of 4 for 1 h was higher than that after the application of ACV-Hex supersaturated system with DS less than 4 or without HPMC E 3. In addition ，the concentration of ACV in the basal epidermis （skin thickness was 100-160 mm）by supersaturated system was significantly higher than that of the marketed aciclovir cream （P＜0.05）. CONCLUSIONS：ACV-Hex，the lipophilic prodrug of ACV ，can form stable supersaturated system with DS of 4 in 10％ propylene glycol-water system in the presence of HPMC E 3. High concentration of ACV could be accumulated in the basal epidermis after the skin was exposed to supersaturated system for 1 h，which may be valuable for local treatment skin infection of herpes simplex virus .

Influencing factors of death in intensive care unit patients with acute respiratory distress syndrome combined with acute kidney injury after continuous renal replacement therapy / 中华肾脏病杂志

Objective:To analyze the influencing factors of death in patients with acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI) in intensive care unit (ICU) after continuous renal replacement therapy (CRRT).Methods:The demographic and clinical data of ICU patients with ARDS combined with AKI after CRRT at Henan Provincial People's Hospital from January 1, 2018 to December 31, 2018 were collected. According to the final treatment results of this hospitalization, the patients were divided into death group and survival group. Survival was defined as the improved patient's condition and hospital discharge. Death was defined as the patient's death during the ICU hospitalization or confirmed death after abandoning treatment and automatically being discharged from the hospital in the follow-up. The basic clinical characteristics and CRRT status between the two groups were compared. Multivariate logistic regression method was used to analyze the influencing factors of death in patients.Results:A total of 132 patients were enrolled, of which 90 patients (68.2%) died, with 84 males (63.6%) and median age of 59(45, 73) years. Compared with the survival group, the death group had higher age, proportion of malignant tumors, sequential organ failure assessment (SOFA) score, number of organ dysfunction and proportion of positive balance of fluid accumulation at 72 hours, longer time from entering ICU to CRRT, and lower mean arterial pressure (minimum value) and oxygenation index (all P<0.05). Multivariate logistic regression analysis results showed that the age≥60 years old ( OR=4.382, 95% CI 1.543-12.440, P=0.006), large number of organ dysfunction ( OR=1.863, 95% CI 1.109-3.130, P=0.019), high SOFA score ( OR=1.231, 95% CI 1.067-1.420, P=0.004) and long time from ICU admission to CRRT ( OR=1.224, 95% CI 1.033~1.451, P=0.020) were independent influencing factors of death in patients with ARDS combined with AKI after CRRT, and high oxygenation index ( OR=0.992, 95% CI 0.986-0.998, P=0.010) was an independent protective factor for patients' prognosis. Conclusions:The mortality of patients with ARDS combined with AKI after CRRT is still high. The age≥60 years old, large number of organ dysfunction, high SOFA score and long time from ICU admission to CRRT are independent influencing factors for death, and high oxygenation index is an independent protective factor for prognosis in patients with ARDS combined with AKI after CRRT.

Establishment of endometriotic models: the past and future / 中华医学杂志(英文版)

Endometriosis is a prevalent chronic disease that affects approximately 6% to 10% of reproductive-aged women. Although numerous researchers have endeavored to explore the etiology of endometriosis over a century, its etiology still remains an enigma. The exploration of pathophysiologic mechanism and novel therapy for endometriosis depends on ideal endometriotic models. In the previous decade, various endometriotic models have been established; therefore, we made a conclusion for available information on these models. This review summarized the common experimental models used in endometriotic studies, including their origins, characteristics, applications, and limitations. Endometriotic models played an important role in studying etiologies and novel treatments of endometriosis during the last decades. Among them, animal models and endometriotic cell lines were viewed as most common studying tools to explore the intrinsic entities of endometriosis. In addition, endometrial organoid also emerged and was regarded as an ideal studying tool for endometriosis research. Different research models collectively complement each other to advance the endometriosis research. The successful establishment of endometrial organoids means that organoids are expected to become an ideal model for studying endometriosis in the future.

Chemical constituents from pericarpium of Metaplexis japonica / 中草药

Objective: To study the chemical constituents from the pericarpium of Metaplexis japonica. Methods: The petroleum ether, dichloromethane and ethyl acetate fractions of 95% ethanol extract from M. japonica were isolated and purified by silica gel, Sephadex LH-20, MPLC and preparative HPLC, etc. The structures of the obtained compounds were identified by physicochemical properties and spectral data. Results: Ten compounds were isolated and identified as (15β,21α)-dihydroxypregna-17,20-trimethylene oxide-4,6-dien-3-one (1), 25-hydroperoxycyc-loart-23-en-3β-ol (2), α-amyrin (3), scoparone (4), aleuritin (5), syringaresinol (6), pergularin-3-O-β-D-oleanodropyranose (7), (20β)-21-dihydroxypregna-4,6-dien-3-one (8), blumenol A (9) and 4-pregnen-20,21- diol-3-one (10). Conclusion: Compound 1 is a new C21 steroidal compound named metajapogenin F, compounds 2 and 10 are isolated from the genus Metaplexis for the first time, and compound 8 is isolated from this plant for the first time.

The current situation and relevant risk factors for disability and dementia in the elderly in urban areas of Jiangsu Province / 中华老年医学杂志

Objective To study the current situation and relevant risk factors for disability and dementia among the elderly in urban areas of Jiangsu province.Methods A stratified cluster sampling method was used to select representative elderly people aged 60 years and over in urban areas in Jiangsu Province,and a face-to-face questionnaire survey was conducted.The activities of daily living (ADL) scale and mini-mental state examination(MMSE) were used to assess the status of disability and dementia.And the relevant risk factors for disability and dementia were analyzed by univariate and multivariate Logistic regression methods.Results A total of 1 600 elderly people were investigated and 1 514 valid questionnaires were recovered.The effective recovery rate was 94.6％.The rates of disability and dementia were 17.9 ％ (271/1 514) and 8.5 ％ (129/1 514) respectively in the elderly in Jiangsu urban areas.Univariate analysis showed that age,marital status,education level,empty-nest,whether or not to suffer from chronic diseases,health status,medication,and whether or not to have dementia were significantly related with the disability in the elderly(P ＜0.01).And age,gender,marital status,education level,whether or not to suffer from chronic diseases,health status,medication,and whether or not to have disability were significantly related with the dementia in the elderly(P ＜ 0.01).Multivariate analysis showed that the risk factors associating with increasing disability in the elderly were advanced age(OR =16.371),non-marriage(OR =1.917),chronic disease (OR =2.256),poor health condition(OR =23.214),dementia (OR =4.067) and insufficient income (OR =1.607)(P＜0.05).And the factors associating with increasing risks for dementia in the elderly were advanced age(OR =2.864),female(OR =1.610),poor health condition(OR =3.097),empty nest (OR =1.607) and disability (OR =4.026) (P ＜ 0.05).Therefore,comprehensive measures should be taken for intervention of disability and dementia in the elderly.Conclusions The incidence of disability and dementia is high among the elderly in urban areas of Jiangsu Province.Disability and dementia are the results of the interaction effect of health,family and social factors.Therefore,comprehensive measures against risk factors should be taken for intervention of disability and dementia in the elderly.

The current situation and relevant risk factors for disability and dementia in the elderly in urban areas of Jiangsu Province / 中华老年医学杂志

Objective@#To study the current situation and relevant risk factors for disability and dementia among the elderly in urban areas of Jiangsu province.@*Methods@#A stratified cluster sampling method was used to select representative elderly people aged 60 years and over in urban areas in Jiangsu Province, and a face-to-face questionnaire survey was conducted.The activities of daily living(ADL)scale and mini-mental state examination(MMSE)were used to assess the status of disability and dementia.And the relevant risk factors for disability and dementia were analyzed by univariate and multivariate Logistic regression methods.@*Results@#A total of 1 600 elderly people were investigated and 1 514 valid questionnaires were recovered.The effective recovery rate was 94.6%.The rates of disability and dementia were 17.9%(271/1 514)and 8.5%(129/1 514)respectively in the elderly in Jiangsu urban areas.Univariate analysis showed that age, marital status, education level, empty-nest, whether or not to suffer from chronic diseases, health status, medication, and whether or not to have dementia were significantly related with the disability in the elderly(P<0.01). And age, gender, marital status, education level, whether or not to suffer from chronic diseases, health status, medication, and whether or not to have disability were significantly related with the dementia in the elderly(P<0.01). Multivariate analysis showed that the risk factors associating with increasing disability in the elderly were advanced age(OR=16.371), non-marriage(OR=1.917), chronic disease(OR=2.256), poor health condition(OR=23.214), dementia(OR=4.067)and insufficient income(OR=1.607)(P<0.05). And the factors associating with increasing risks for dementia in the elderly were advanced age(OR=2.864), female(OR=1.610), poor health condition(OR=3.097), empty nest(OR=1.607)and disability(OR=4.026)(P<0.05). Therefore, comprehensive measures should be taken for intervention of disability and dementia in the elderly.@*Conclusions@#The incidence of disability and dementia is high among the elderly in urban areas of Jiangsu Province.Disability and dementia are the results of the interaction effect of health, family and social factors.Therefore, comprehensive measures against risk factors should be taken for intervention of disability and dementia in the elderly.