PON-Fold: Prediction of Substitutions Affecting Protein Folding Rate.

Most proteins fold into characteristic three-dimensional structures. The rate of folding and unfolding varies widely and can be affected by variations in proteins. We developed a novel machine-learning-based method for the prediction of the folding rate effects of amino acid substitutions in two-state folding proteins. We collected a data set of experimentally defined folding rates for variants and used them to train a gradient boosting algorithm starting with 1161 features. Two predictors were designed. The three-class classifier had, in blind tests, specificity and sensitivity ranging from 0.324 to 0.419 and from 0.256 to 0.451, respectively. The other tool was a regression predictor that showed a Pearson correlation coefficient of 0.525. The error measures, mean absolute error and mean squared error, were 0.581 and 0.603, respectively. One of the previously presented tools could be used for comparison with the blind test data set, our method called PON-Fold showed superior performance on all used measures. The applicability of the tool was tested by predicting all possible substitutions in a protein domain. Predictions for different conformations of proteins, open and closed forms of a protein kinase, and apo and holo forms of an enzyme indicated that the choice of the structure had a large impact on the outcome. PON-Fold is freely available.

Salvianolic acid B promotes the invasion and migration of HO-induced HTR-8/Svneo trophoblast cells by upregulating matrix metalloproteinase-9 the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway.

OBJECTIVE: To elucidate the regulatory effects of salvianolic acid B (SalB) on trophoblast cells in preeclampsia (PE). METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenylte-trazolium bromide (MTT) assays were used to detect the viability of human extravillous trophoblast HTR-8/Svneo cells induced by HO following treatment with different concentrations of SalB. The levels of oxidative stress-related molecules, including superoxide dismutase, glutathione-Px and malondialdehyde were detected using corresponding kits. Cell apoptosis was detected using a Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay, and the expression of apoptosis-related proteins was detected using western blot analysis. In the present study, wound healing and Transwell assays were performed to measure the levels of cell invasion and migration. Western blot analysis was also used to detect the expression levels of epithelial-mesenchymal transition-related proteins. The mechanisms underlying SalB were further investigated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis, to determine the expression levels of matrix metallopeptidase 9 (MMP-9) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt). RESULTS: SalB increased the activity of HTR-8/Svneo cells, inhibited oxidative damage and promoted the invasion and migration of trophoblast cells induced by HO. Furthermore, the expression levels of MMP-9 and members of the PI3K/Akt signaling pathway were significantly decreased. The pathway agonist, LY294002, and MMP-9 inhibitor, GM6001, reversed the effects of SalB on HO-induced cells. CONCLUSIONS: SalB promoted the invasion and migration of HO-induced HTR-8/Svneo trophoblast cells by upregulating MMP-9 the PI3K/Akt signaling pathway.

Pharmacologic and non-pharmacologic interventions for emotional lability: A meta-analysis.

Emotional Lability (EL) is a common symptom dimension in a variety of psychiatric disorders. However, as it is not typically a diagnosis in its own right, it lacks a consistently applied clinical definition and treatment approach. Therefore, in this review we performed a meta-analysis to determine the effect sizes for treatments of EL across diagnostic categories. We then conducted subgroup analyses to compare effect sizes for pharmacologic (MED) and behavioral (BEH) treatments, according to underlying diagnosis, and according to medication class. We found that pharmacologic and non-pharmacologic treatments are effective for EL, and that the effect sizes were similar - a finding with implications for clinical practice. Our findings also support future research which approaches EL as an important construct independent of underlying diagnosis.

Comparison of disinfection quality in nurseries of Nanjing during 2019-2021 / 中国学校卫生

Objective@#To analyze the disinfection quality and influencing factors of nurseries in Nanjing during 2019-2021, so as to provide a scientific basis for optimizing preventive disinfection strategies and measures in nurseries.@*Methods@#Environmental samples from 389 nurseries in Nanjing from January 2019 to December 2021 were tested, and the change of disinfection quality qualification rate was compared.@*Results@#The overall disinfection qualification rate of nurseries of year 2019-2021 were 96.32%, 95.85% and 94.60%, respectively, showing a downward trend ( χ 2 trend =8.67, P <0.05). Specifically, disinfection qualification rate of object surfaces, staff hands and tableware showed a downward trend, while the disinfection qualification rate of dynamic air showed an upward trend, and the differences were statistically significant ( χ 2 trend =23.17, 12.32, 5.37, 21.48, P <0.05). The total qualification rate of disinfection in Jiangning and Liuhe districts increased during 2019-2021( χ 2 trend =21.46, 24.05, P <0.05).@*Conclusion@#Disinfection quality of nurseries in Nanjing has declined by year during 2019-2021, especially the object surfaces and staff hands. It is urgent to optimize and refine the strategies and measures for preventive disinfection in nurseries, strengthen the training of personnel on disinfection knowledge, and ensure the quality of disinfection in nurseries.

New progress and challenges in the diagnosis and treatment of cosmetic allergy-related adverse reactions / 中华预防医学杂志

In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.

Hotspots and difficulties of biliary surgery in older patients / 中华医学杂志(英文版)

With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.

Research hotspots and trends of artificial intelligence in diabetic retinopathy based on bibliometrics and high-impact papers / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze research hotspots and trends of artificial intelligence in diabetic retinopathy(DR)based on bibliometrics and high-impact papers.METHODS: Papers on artificial intelligence in DR research published in the Web of Science Core Collection(WoSCC)from January 1, 2012, to December 31, 2022 were retrieved. The data was analyzed by CiteSpace software to examine annual publication number, countries, institutions, source journal, research categories, keywords, and to perform an in-depth analysis of high-impact papers.RESULTS: A total of 1 009 papers on artificial intelligence in DR from 79 countries were included in the study, with 272 papers published in 2022. Notably, China and India contributed 287 and 234 papers, respectively. The United Kingdom exhibited a centrality score of 0.31, while the United States boasted an impressive H-index of 48. Three prominent institutions in the United Kingdom(University of London, Moorfields Eye Hospital, and University College London)and one institution in Egypt(Egyptian Knowledge Bank)all achieved a notable H-index of 14. The primary academic disciplines associated with this research field encompassed ophthalmology, computer science, and artificial intelligence. Burst keywords in the years 2021～2022 included transfer learning, vessel segmentation, and convolutional neural networks.CONCLUSION: China emerged as the leading contributor in terms of publication number in this field, while the United States stood out as a key player. Notably, Egyptian Knowledge Bank and University of London assumed leading roles among research institutions. Additionally, IEEE Access was identified as the most active journal within this domain. The research focus in the field of artificial intelligence in DR has transitioned from AI applications in disease detection and grading to a more concentrated exploration of AI-assisted diagnostic systems. Transfer learning, vessel segmentation, and convolutional neural networks hold substantial promise for widespread applications in this field.

Research progress of microglia regulating phagocytosis of apoptotic neurons after intracerebral hemorrhage / 中华神经科杂志

Intracerebral hemorrhage is the bleeding caused by spontaneous non-traumatic rupture of blood vessels in brain parenchyma. It has high disability rate and mortality. A series of injuries after intracerebral hemorrhage will lead to neuronal apoptosis. If apoptotic neurons are not cleared in time, intracellular toxic substances will be released, thereby further aggravating the inflammatory reaction. Therefore, the timely clearance of apoptotic cells is of great significance to the brain homeostasis after intracerebral hemorrhage. At the same time, a large number of phagocytic "eat me" signal phosphatidylserine (PS) will appear on the surface of apoptotic neurons. Microglia, as resident macrophages in the brain, have a variety of PS receptors on their surface, which promote the phagocytosis of apoptotic neurons by microglia and reduce the occurrence of local inflammatory responses.

Exploration of critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases / 中华老年医学杂志

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

PPARγ2 functions as a tumor suppressor in a translational mouse model of human prostate cancer / 亚洲男科学杂志(英文版)

Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.

Hematoma regression: a therapeutic target for intracerebral hemorrhage / 国际脑血管病杂志

The disability and mortality rate of patients with intracerebral hemorrhage are very high. At present, there is no effective treatment to improve the outcome of patients with intracerebral hemorrhage. Mechanical compression of hematoma and release of toxic products are the main causes of primary and secondary brain injury in patients with intracerebral hemorrhage, while safe and effective acceleration of hematoma regression is the key strategy to improve the neurological deficit in patients with intracerebral hemorrhage. Microglia/macrophages are the main phagocytic system that mediates hematoma clearance and are mainly polarized into M1 and M2 phenotypes. Cell surface receptors and possible signal transduction pathways play an important role in regulating the endogenous hematoma regression mediated by microglia/macrophages, and may become a new target for clinical treatment of intracerebral hemorrhage and improvement of the outcomes of patients in the future.

Safety and effectiveness of topical application of tranexamic acid to reduce drainage of elderly femoral neck fractures after total hip arthroplasty / 中国组织工程研究

BACKGROUND: Topical application of tranexamic acid can reduce the drainage after total hip arthroplasty for degenerative diseases. However, there are few reports on the application of tranexamic acid in primary total hip arthroplasty for simple elderly femoral neck fracture. OBJECTIVE: To analyze the safety and effectiveness of topical application of tranexamic acid to reduce drainage of elderly femoral neck fractures after total hip arthroplasty. METHODS: Forty-five elderly femoral neck fractures patients undergoing total hip arthroplasty in the Zhengzhou People’s Hospital from January to December 2019 were enrolled in this study, including 19 males and 26 females at the age of 59-82 years old. Twenty-one patients in the observation group were injected with tranexamic acid retrogradely through the drainage tube after total hip arthroplasty. Twenty-four patients in the control group were injected with normal saline retrogradely through the drainage tube after total hip arthroplasty. The postoperative drainage volume and adverse events were recorded; the wound healing was closely observed; and the coagulation function was checked. This study was approved by the Medical Ethics Committee of Zhengzhou People’s Hospital. RESULTS AND CONCLUSION: (1) All patients’ incisions healed grade A, and no myocardial infarction, cerebral infarction, pulmonary embolism, or deep vein thrombosis of the lower extremities occurred. (2) At postoperative 3 days, total drainage and hemoglobin loss were less in the observation group than those in the control group (P 0.05). (4) Results suggested that topical application of tranexamic acid in total hip arthroplasty for elderly femoral neck fractures is safe and effective. It can significantly reduce postoperative drainage without affecting coagulation function.

Functional discovery and production technology for natural bioactive peptides / 生物工程学报

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.

Technology development and instrumentation of a high-throughput and automated microbial microdroplet culture system for microbial evolution and screening / 生物工程学报

Since microdroplets are able to be generated rapidly in large amount and each droplet can be well controlled as an independent micro-cultivator, droplet microfluidic technology can be potentially used in the culture of microorganisms, and provide the microbial culture with high throughput manner. But its application mostly stays in the laboratory-level building and using for scientific research, and the wide use of droplet microfluidics in microbial technology has been limited by the key problems that the operation for microdroplets needs high technical requirements with wide affecting factors and the difficulties in integration of automatic microdroplet instrumentation. In this study, by realizing and integrating the complicated operations of droplet generation, cultivation, detection, splitting, fusion and sorting, we design a miniaturized, fully automated and high-throughput microbial microdroplet culture system (MMC). The MMC can be widely used in microbial growth curve test, laboratory adaptive evolution, single factor and multi-level analysis of microbial culture, metabolite detection and so on, and provide a powerful instrument platform for customized microbial evolution and screening aiming at efficient strain engineering.

Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase / 国际口腔科学杂志·英文版

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

SARS-CoV-2 seroprevalence and detection fraction in Utah urban populations from a probability-based sample

This projects aim was to generate an unbiased estimate of the incidence of SARS-CoV-2 infection in four urban counties in Utah. A multi-stage sampling design was employed to randomly select community-representative participants 12 years and over. Between May 4 and June 30, 2020, surveys were completed and sera drawn from 8,108 individuals belonging to 5,125 households. A qualitative chemiluminescent microparticle immunoassay was used to detect the presence of IgG antibody to SARS-CoV-2. The overall prevalence of IgG antibody to SARS-CoV-2 was estimated at 0.8%. The estimated seroprevalence-to-case count ratio was 2.4, corresponding to a detection fraction of 42%. Only 0.2% of individuals who had a nasopharyngeal swab collected were reverse transcription polymerase chain reaction (RT-PCR) positive. The prevalence of antibodies to SARS-CoV-2 in Utah urban areas between May and June was low and the prevalence of positive RT-PCR even lower. The detection fraction for COVID-19 in Utah was comparatively high. Article SummaryProbability-based sampling provides an effective method for robust estimates of community-based SARS-CoV-2 seroprevalence and detection fraction among urban populations in Utah.

Chirality of the biomolecules enhanced its stereospecific action of dihydromyricetin enantiomers.

The present study explores the effect of chirality of the biological macromolecules, its functional aspects, and its interaction with other food components. Dihydromyricetin (DHM) is a natural novel flavonol isolated from the vine tea (Ampelopsis grossedentata) leaves. However, limited progress in enantiopure separation methods of such compounds hinder in the development of enantiopure functional studies. This study is an attempt to develop a simple, accurate, and sensitive extraction method for the separation of the enantiopure DHM from vine tea leaves. In addition, the identification and purity of the extracted enantiopure (-)-DHM were further determined by the proton nuclear magnetic resonance (1H-NMR) and the carbon nuclear magnetic resonance (13C-NMR). The study further evaluates the antimicrobial activity of isolated (-)-DHM in comparison with racemate (+)-DHM, against selected foodborne pathogens, whereas the action mode of enantiopure (-)-DHM to increase the integrity and permeability of the bacterial cell membrane was visualized by confocal laser scanning microscopy using green fluorescence nucleic acid dye (SYTO-9) and propidium iodide (PI). Moreover, the morphological changes in the bacterial cell structure were observed through field emission scanning electron microscope. During analyzing the cell morphology of B. cereus (AS11846), it was confirmed that enantiopure (-)-DHM could increase the cell permeability that leads to the released of internal cell constituents and, thus, causes cell death. Therefore, the present study provides an insight into the advancement of enantiopure isolation along with its antimicrobial effect which could be served as an effective approach of biosafety.

Shikonin induces cell death by inhibiting glycolysis in human testicular cancer I-10 and seminoma TCAM-2 cells / 南方医科大学学报

OBJECTIVE@#To investigate the pattern of shikonin-induced cell death in testicular cancer cell I-10 and seminoma TCAM-2 cells and explore the possible mechanism in light of mitochondrial function and glycolysis.@*METHODS@#I-10 cells treated with 0, 1.2, 1.4 and 1.6 μmol/L shikonin and TCAM-2 cells treated with 0, 0.5, 1 and 1.5 μmol/L shikonin were examined for mitochondrial membrane potential and production of reactive oxygen species (ROS) using JC-1 kit and ROS kit, respectively. The levels of intracellular lactic acid in the cells were detected using a lactic acid kit. The inhibitory effect of shikonin on the proliferation of the cells was assessed with MTT assay. The death patterns of the cells were observed by transmission electron microscopy, and annexin V-FITC/PI double staining was used to detect cell apoptosis. Western blotting was used to detect the relative expression levels of the apoptotic proteins Bax, Bcl-2, and cleaved caspase-3, the autophagy- related protein LC3B and glycolysis- related proteins PKM2, GLUT1 and HK2.@*RESULTS@#MTT assay showed that shikonin significantly inhibited the proliferation of I-10 and TCAM-2 cells in a time- and dose-dependent manner ( < 0.05). The IC values of shikonin in I-10 cells at 24, 48, and 72 h were 1.8, 1.36 and 1.16 μmol/L, as compared with 2.37, 0.8 and 0.41 μmol/L in TCAM-2 cells, respectively. Shikonin treatment significantly reduced mitochondrial membrane potential, increased ROS levels and lower the level of lactic acid in both I-10 and TCAM-2 cells ( < 0.05). Transmission electron microscopy and annexin V-FITC/PI double staining demonstrated that shikonin induced apoptosis and excessive autophagy in I-10 and TCAM-2 cells ( < 0.05). In both I-10 and TCAM cells, shikonin treatment significantly down- regulated the expressions of Bax, Bcl-2, cleaved caspase-3, PKM2, GLUT1 and HK2, and up-regulated the expression of autophagy-related protein LC3B ( < 0.05).@*CONCLUSIONS@#Shikonin can inhibit the proliferation, induce apoptosis and increase autophagy in both I-10 and TCAM-2 cells probably by affecting energy metabolism of the cells.

Preventive and therapeutic measures to improve perioperative safety in extremely elderly patients with biliary diseases / 中华肝胆外科杂志

Objective To study protective and therapeutic measures to improve perioperative safety in extremely elderly patients with biliary diseases.Methods A retrospective case-control study was conducted.The clinical data of elderly patients with biliary diseases treated at the Department of General Surgery,Beijing Electric Power Hospital,from July 2013 to December 2018,were collected.According to age,the patients were divided into the high age (HA) group (≥80.0 years) and the middle-low age (MLA) group (60.0～79.0 years).The related indexes of perioperative safety such as preoperative coexisting diseases,functions of liver,kidney,heart and lung,surgical procedures,intraoperative blood loss,operation time,postoperative hospital stay and postoperative hospital stay were analyzed and compared between the two groups.Results Of the 372 included patients,there were 168 males and 204 females,aged 60.0 to 96.0 (72.0 ± 8.6) years.There were 69 elderly patients (37 males and 32 females) aged 80.0 to 96.0 (84.4 ±3.8) years in the HA group.There were 303 patients in the middle and lower age group (131 men and 172 women),aged 60.0 to 79.0(68.4 ±5.8) years (MLA group).(1) Preoperative coexisting diseases were significantly increased in the HA compared with the MLA group (all P ＜ 0.05),including the proportion of coexisting coronary heart disease [34.8％ (24/69) vs.18.5％ (56/303)],hypertension [68.1％ (47/69)vs.46.9％ (142/303)],chronic bronchitis with emphysema [17.4％ (12/69) vs.3.6％ (11/303)],hypoproteinemia [39.1％ (27/69) vs.26.7％ (81/303)],and anemia [42.0％ (29/69) vs.11.9％ (36/303)].(2) Laboratory examinations:the functions of liver,kidney,heart,lung and blood coagulation were significantly worse in the HA compared with the MLA group (P ＜ 0.05).(3) Surgical procedures:the proportion of open cholecystectomy with transcystic common bile duct exploration (OC + OTCBDE) was higher [17.4％ (12/69) vs.6.9％ (21/303)],while laparoscopic cholecystectomy (LC) was lower [43.5％ (30/69) vs.62.7％ (190/303)],in the HA compared with the MLA group (P ＜0.05,totally).(4) Operative effects:the intraoperative blood loss [30.0 (20.0,75.0) ml vs.20.0 (10.0,30.0) ml],operation time [90.0(72.5,137.5) min vs.77.0(55.0,115.0) min],postoperative hospital stay [10.0(6.0,18.0) d vs.7.0(4.0,11.0) d],and length of hospitalization [17.0(11.5,23.0) d vs.13.0(9.0,19.0) d] were significantly increased or prolonged in the HA compared with the MLA group (all P ＜0.05).(5) Postoperative complications:the incidence of postoperative complications was significantly higher [30.4％ (21/69) vs.12.2％ (37/303)] in the HA compared with the MLA group (P ＜ 0.05).(6) Therapeutic outcomes:there was a cure rate of 95.7％ (66/69) in the HA group,and 97.7％ (296/303)in the MLA group.No significant difference in the therapeutic effects was found between the two groups (P ＞ 0.05).Conclusions Operation in extremely elderly patients with biliary diseases is safe and feasible.The key is to take measures such as actively treating preoperative coexisting diseases,strictly mastering operative indications,reasonably selecting surgical procedures,accurately carrying out precise operation,strictly monitoring and dealing with intraoperative emergency,timely preventing and treating postoperative complications,and especially focusing on maintaining cardiopulmonary function during the perioperative period.

Effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal axis, as well as learning and memory function in female offspring rats after chronic stress / 中华行为医学与脑科学杂志

Objective:To investigate the effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal(HPA) axis and learning and memory function in female offspring rats.Methods:Pregnant rats were divided into treatment group and control group by a table of random numbers, which were given fluoxetine (10 mg/kg per day) or the same amount of normal saline at 11-20 days of gestation, respectively.Ten female offspring from each group were selected randomly for open field, electrical maze and object recognition tests at 12 weeks after birth, and the concentrations of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined.Then they were given an unpredictable chronic stress (UCS) for 21 days, and the previous experiments were repeated.Finally, rats were sacrificed and the hypothalamus tissues were taken to measure the mRNA expression of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP). SPSS 19.0 was used for data describing and t-test. Results:Before UCS, there were no significant differences between the two groups among all the indexes(all P>0.05). After UCS, the horizontal movement and vertical movement of the rats in the two groups were significantly reduced compared with that before treatment, and the horizontal movement of the rats in the treatment group ((37.2±7.2) vs (50.8±8.5), t=4.73, P<0.01) and vertical movement ((10.6±2.0) vs (15.2±5.1), t=2.93, P<0.05) were lower than those in the control group.The correct reaction times decreased and the total reaction time increased in the two groups.While the correct response times of the treatment group were significantly lower than that of the control group (3.4±1.5) vs (4.5±0.9), t=2.36, P<0.05). The object recognition index of the rats in the treatment group decreased significantly compared with the control group ((0.11±0.04) vs (0.16±0.05), t=2.28, P<0.05). Before and after UCS, the change rate of ACTH ((61.13±26.08)% vs (29.83±12.73)%, t=3.67, P<0.01) and CORT ((105.71±18.39)% vs (74.15±39.24)%, t=2.34, P<0.05) in the treated group was significantly higher than that in the control group, and the mRNA expression of CRH in hypothalamus was significantly higher than that in the control group ( t=4.15, P<0.01). Conclusion:No significant damage is found to the HPA axis as well as learning and memory function of female offspring rats after exposure to fluoxetine in pregnancy, but the susceptibility of HPA axis as well as learning and memory function is increased under chronic stress.