Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats.

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action. METHODS: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis. RESULTS: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons. CONCLUSION: The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

Effects of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方） on Dendritic Spines of Hippocampal Dentate Gyrus and Wnt5a/RhoA Signaling Pathway in Diabetic with Depression Model Rats / 中医杂志

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

Acute effects of air pollution on pulmonary function and exhaled nitric oxide in children in Shanghai / 上海预防医学

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM2.5， PM10， SO2， NO2， O3 and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM2.5， PM10， SO2 and NO2 were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P<0.05）. PM2.5， PM10 and NO2 were negatively correlated with the changes of lung function FEF25%， FEF50%， FEF75%， FeF25%-75%， PEF， FVC， FEV1 and FEV1/FVC， and the effect was reflected in lag0 to lag3 days （P<0.05）. The results of the dual pollutant model showed that the concentration changes of SO2 and NO2 were significantly correlated with the decrease of FEV1 when combined with O3 or PM2.5 （P<0.01）， and the concentration changes of PM2.5 was significantly correlated with the increase of FeNO when O3， SO2 and NO2 were combined respectively （P<0.01）. The effects of the dual pollutant model were greater than the effect of PM2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer， it still has an impact on children’s respiratory tract function index and inflammation index， and the combined effect of dual pollutants is more significant than that of single pollutant.

Predictive value of serum thrombospondin-1,D-dimer and tissue inhibitor of metalloproteinase-1 levels in late pregnancy for postpartum hemorrhage in re-pregnant women with scarred uterus / 新乡医学院学报

Objective To investigate the predictive value of serum thrombospondin-1(THBS-1),D-dimer(D-D)and tissue inhibitor of metalloproteinase-1(TIMP-1)levels in late pregnancy for postpartum hemorrhage(PPH)in re-pregnant women with scarred uterus.Methods Totally 108 re-pregnant women with scarred uterus admitted to the First Affiliated Hospital of Xinxiang Medical University from June 2020 to August 2022 were selected and divided into the PPH group(n=21)and the non-PPH group(n=87)according to whether PPH occurred after delivery.On the day of admission,5 mL elbow venous blood was collected from re-pregnant women in the two groups,and the levels of serum THBS-1,D-D and TIMP-1 of pregnant women in the two groups were detected by enzyme-linked immunosorbent assay.The serum THBS-1,D-D TIMP-1 levels and clinical data of pregnant women between the two groups were compared.The influencing factors on the occurrence of PPH in re-pregnant women with scarred uterus were analyzed by multivariate logistic regression,and the predictive value of serum THBS-1,D-D and TIMP-1 levels on the occurrence of PPH in re-pregnant women with scarred uterus was evaluated by receiver operating characteristic curve.Results The percentage of patients with ≥ 2 induced abortions,placental abruption,uterine incision laceration,uterine inertia or scar thickness＜0.3 cm,as well as serum THBS-1 and D-D levels in late pregnancy in the PPH group were significantly higher than those in the non-PPH group,and serum TIMP-1 level in late pregnancy were significantly lower than that in the non-PPH group(P＜0.05).The uterine inertia,as well as high D-D and THBS-1 levels,were independent risk factors for PPH in re-pregnant women with scarred uterus(P＜0.05),and low TIMP-1 level was a protective factor(P＜0.05).The area under the curve of combined serum THBS-1,D-D and TIMP-1 levels to predict PPH in re-pregnant women with scarred uterus was greater than that predicted by the three factors alone(P＜0.05).Conclusion Serum THBS-1,D-D and TIMP-1 levels in late pregnancy can be used as reference indicators for predicting the occurrence of PPH in re-pregnant women with scarred uterus,and the combination of the three indexes is more effective in predicting the occurrence of PPH.

Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.

Traditional Chinese Medicine in Treatment of Diabetic Kidney Disease Based on Wnt/β-catenin Signaling Pathway： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is a common complication of diabetes and a leading cause of end-stage kidney disease. Its pathogenesis is complex， and it presents a significant challenge in treatment， gradually becoming a major global public health issue. One of the main pathological changes in DKD is tubulointerstitial fibrosis， clinically characterized by proteinuria and declining kidney function， which severely impacts the daily life of patients. Currently， western medicine commonly uses methods such as controlling blood sugar and blood pressure， and reducing proteinuria to treat DKD， but the efficacy is unsatisfactory， and there are many side effects. As reported， traditional Chinese medicine （TCM） treatment for DKD has many advantages， such as low cost， significant efficacy， and minimal adverse reactions. More researchers focusing on DKD are turning their attention to TCM， and progress has been made in related studies both in China and abroad. The Wnt/β-catenin signaling pathway is relatively evolutionarily conserved and plays a crucial role in normal biological development and the entire life process. Studies have demonstrated that abnormal activation of the Wnt/β-catenin signaling pathway is related to renal fibrosis， which coincides with TCM theory of "collateral diseases". By reviewing relevant literature， this article reviewed the Wnt/β-catenin signaling pathway and its role in DKD and summarized the research status of TCM monomers， single drug extracts， and TCM formulas in improving renal fibrosis and treating DKD through the improvement of glomerular mesangial cells， renal tubular epithelial cells， and podocyte injury， aiming to provide new ideas and directions for TCM treatment of DKD.

Study on Anti-Depression Active Ingredients of Bupleuri Radix Based on UPLC-Q-TOF/MS Integrated with CORT-Induced Poorly Differentiated PC12 Depression Cell Model / 世界科学技术-中医药现代化

Objective To analyze the chemical constituents in the water extract of Bupleuri Radix and investigate the active ingredients of Bupleuri Radix for the treatment of depression.Methods The chemical constituents in the water extract of Bupleuri Radix were identified by Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).CORT-induced poorly differentiated PC12 depression cell model was launched,and PC12 cells were pretreated with monomeric compounds from Bupleuri Radix for 24 h.The cell viability and LDH release rate were measured by CCK-8 assy kit and LDH assay kit,respectively.Results A total of 53 compounds were identified in the water extract of Bupleuri Radix,mainly including type Ⅰ,type Ⅱ and type Ⅲsaikosaponins.Among them,saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin E,saikosaponin F and 6″-acetyl saikosaponin A contributed the most to the metabolite profile of Bupleuri Radix,and could improve the viability of CORT-induced PC12 cells(P<0.05,P<0.01).Furthermore,saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin E and saikosaponin F could decrease the LDH release rate of CORT-induced PC12 cells(P<0.05,P<0.01).Conclusion The major anti-depression active ingredients in Bupleuri Radix may be Saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin E and saikosaponin F,which lays a foundation for the research of the quality control and pharmacodynamic material basis of Bupleuri Radix.

Risk factors of cardiovascular and cerebrovascular diseases in young patients with hyperhomocysteinemia / 中国基层医药

Objective:To investigate the risk factors of cardiovascular and cerebrovascular diseases in young patients with hyperhomocysteinemia.Methods:A total of 260 patients younger than 45 years old who received treatment at the Department of Emergency, Seventh Medical Center, Chinese PLA General Hospital from January 2018 to January 2019 were included in this study. Among these patients, 126 patients with serum homocysteine levels ≥ 15.0 μmol/L were included in the hyperhomocysteinemia group, and 134 patients with serum homocysteine levels < 15.0 μmol/L were included in the control group. Height, body weight, body mass index, blood pressure, homocysteine, fasting blood glucose, blood uric acid, total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and N-terminal B-type natriuretic peptide were determined in each group. Changes in risk factors of cardiovascular and cerebrovascular diseases were compared between the hyperhomocysteinemia and control groups.Results:There were significant differences in body mass index [(26.42 ± 3.54) kg/m 2vs. (22.14 ± 3.22) kg/m 2, t = 10.21, P = 0.016], blood uric acid [(308.71 ± 78.44) μmol/L vs. (285.05 ± 92.09) μmol/L, t = 2.22, P = 0.027], the incidence of coronary heart disease (73/126 vs. 61/134, χ2 = 4.00, P = 0.045) and the incidence of stroke (19/126 vs. 6/134, χ2 = 8.39, P = 0.004) between the hyperhomocysteinemia and control groups. There were no significant differences in fasting blood glucose, blood lipid level, N-terminal B-type natriuretic peptide, and the incidences of diabetes mellitus and hypertension between the two groups (all P > 0.05). Conclusion:The related risk factors of cardiovascular and cerebrovascular diseases increase in young patients with hyperhomocysteinemia. The incidences of coronary heart disease and stroke are very high, and therefore timely intervention should be carried out.

Effects of Zuogui Pill on osteoclast activity and expression of miR-133b-3p/RhoA in postmenopausal osteoporosis rats / 国际中医中药杂志

Objective:To study the effects of Zuogui Pills on the expressions of miR-133b-3p and RhoA in osteoclasts of postmenopausal osteoporosis rats; To discuss its potential mechanism.Methods:SD female rats were randomly divided into normal group, model group, sham-operation group, and Zuogui Pills group using a random number table method, with 6 rats in each group. The model group and Zuogui Pills group were treated with oophorectomy to construct a rat model of osteoporosis. Zuogui Pills group was orally administered with Zuogui Pills decoction at a concentration of 10 g/kg for 12 consecutive weeks. Colorimetric method was used to measure the serum calcium and phosphorus levels of rats, and ELISA method was used to detect ALP levels. Bone density meter was used to measure the bone density of the femurs of rats in each group. The osteoclast of each group were cultured, and the expressions of RANKL and RUNX2 protein were detected by Western blot. MiRNA sequencing and differential expression analysis were performed on bone tissues of rats. Osteoclasts were treated with miR-133b-3p mimic and its negative control. The cell proliferation activity of osteoclasts was detected by cell counting kit-8 (CCK-8). The osteoclast differentiation activity was detected by the tartrate-resistant acid phosphatase staining. The dual-luciferase reporter assay was used to detect the relationship between miR-133b-3p and RhoA. The "rescue" experiment of miR-133b-3p mimic and RhoA co-expression were used to study the molecular regulatory mechanism of Zuogui Pills on osteoclast activity.Results:Compared with the model group, the bone mineral density of Zuogui Pills group significantly increased ( P<0.05, P<0.01), the levels of calcium and phosphorus in serum increased, the level of alkaline phosphatase ALP decreased ( P<0.05), the expression of RANKL protein decreased, and the expression of RUNX2 protein increased. Sequencing results showed that rno-miR-133b-3p was down-regulated in osteoclasts of postmenopausa osteoporosis rats treated with Zuogui Pills with the maximum difference ( P<0.01). Q-PCR results showed that the expression of miR-133b-3p in osteoclasts of Zuogui Pills group was significantly lower than that of the model group. The upregulation of miR-133b-3p could significantly promote the cell proliferation and differentiation of osteoclasts. RhoA overexpression could reverse the excessive proliferation and differentiation of osteoclasts caused by miR-133b-3p overexpression. Conclusions:RhoA is the target gene regulated by miR-133b-3p. Zuogui Pills can inhibit the activity of osteoclasts by regulating miR-133b-3p/RhoA axis, relieving the symptoms of osteoporosis.

Metabolomic Analysis of Urine in Rat Model with Spleen-stomach Damp-heat Syndrome / 中国实验方剂学杂志

ObjectiveTaking the rat model of spleen-stomach damp-heat syndrome（SSDHS） as the research object， this study aimed to investigate the potential biomarkers of SSDHS and the related metabolic pathways based on urine metabolomics， and tried to reveal the essence of SSDHS at the level of endogenous small molecular metabolites. MethodSixteen SD rats were randomly divided into normal and model groups. The normal group was fed normal chow and the model group was fed with 200 g·L-1 honey water daily， and lard and Chinese Baijiu alternately on alternate days for 17 days. The SSDHS model rats were exposed to external dampness-heat environment with temperature at 30-34 ℃， relative humidity of 95% for 2 h at the same time every day from the 10th day for 7 d. Then， the model was evaluated by observing the general conditions of the rats， measuring the contents of motilin（MTL） and gastrin（GT） in plasma by enzyme-linked immunosorbent assay（ELISA）， and examining the histopathology of gastronitestinal tissues. In additon， the urine metabolomics analysis was performed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， and the detection conditions was as follows：ACQUITY™ UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution （0-3 min， 1%-18%B； 3-8 min， 18%-40%B； 8-10 min， 40%-100%B）， the flow rate of 0.4 mL·min-1， electrospray ionization（ESI） in positive and negative ion modes， scanning range of m/z 50-1 000. The univariate and multivariate statistical analysis were constructed for screening inter-group differential ions， the element composition was calculated according to the precise relative molecular weight， and ion information was matched with databases such as Human Metabolome Database（HMDB） to identify biomarkers. Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to obtain the biological information of metabolites， and their associated metabolic pathways were analyzed by MetaboAnalyst 5.0. ResultCompared with the normal group， the rectal temperature of the model group increased significantly（P<0.01）， the levels of plasma MTL and GT decreased significantly（P<0.05， P<0.01）， and pathological changes such as bleeding， congestion and inflammatory infiltration in the gastric and colonic tissues. A total of 25 differential metabolites such as L-histidine， citric acid and isocitric acid were found to be the potential biomarker of SSDHS by urine metabolomics， 13 of which were phase Ⅱ metabolites of endogenous substances（glucuronic acid conjugates， sulfuric acid conjugates and acetyl conjugates）， involving the metabolic pathways of histidine metabolism， tricarboxylic acid cycle， glyoxylate and dicarboxylate metabolism. ConclusionSSDHS primarily causes disorders of histidine metabolism， tricarboxylic acid cycle， glyoxylate and dicarboxylate metabolism， as well as the imbalance of the activation/inactivation of endogenous metabolites， which may involve the immune response， material and energy metabolism， inflammatory response and intestinal flora， and may provide a basis for the establishment and application of SSDHS model.

Zuogui Jiangtang Jieyu Decoction promotes neural stem cell self-renewal and activates Shh signaling in the hippocampal dentate gyrus of diabetic rats with depression / 南方医科大学学报

OBJECTIVE@#To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression.@*METHODS@#Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting.@*RESULTS@#The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models.@*CONCLUSION@#ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.

DRG medical service performance evaluation based on entropy weight TOPSIS and rank sum ratio method / 中华医院管理杂志

Objective:To evaluate medical service performance of the DRG pilot public hospitals in a city was carried out by using the entropy weight TOPSIS and the rank sum ratio method, so as to provid the decision-making basis for the DRG pilot reform and the high-quality development of public hospitals.Methods:The case-mix index(CMI) value, the number of DRG groups, the time consumption index, the cost consumption index, and the low-risk mortality rate were obtained from the first page of medical records of 21 DRG pilot hospitals in a city from January 2019 to December 2020.The entropy weight TOPSIS method and the rank sum ratio method were used to evaluate the medical services performance of 21 DRG pilot hospitals.Results:The CMI value and the number of DRG groups in 21 DRG pilot hospitals increased from 0.81 and 353 in 2019 to 0.86 and 369 in 2020 respectively, and the time consumption index decreased from 0.98 to 0.92. The entropy weight TOPSIS method and the rank sum ratio method had good consistency and correlation with the hospital performance evaluation results from 2019 to 2020 ( P<0.05). The overall ranking of the performance evaluation of pilot hospitals in 2020 was higher than that in 2019, the tertiary hospitals were higher than secondary hospitals, and hospitals were higher than maternal and child health care hospitals. Conclusions:The DRG payment reform had promoted the quality and efficiency of medical services in the city.

Effects of different preoperative biliary drainage methods on bile bacterial culture and drug resistence of malignant obstructive jaundice / 中华消化外科杂志

Objective:To investigate the effects of different preoperative biliary drainage methods on bile bacterial culture and drug resistence of malignant obstructive jaundice.Methods:The retrospective and descriptive study was conducted. The clinical data of 317 patients with malignant obstructive jaundice who were admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to December 2018 were collected. There were 216 males and 101 females, aged (62±10)years. Of 317 patients, 158 cases had no preoperative biliary drainage, 115 received preoperative biliary drainage by percutaneous transhepatic choledochal drainage (PTCD), 44 received preoperative biliary drainage by endoscopic retrograde biliary drainage (ERBD). Observation indicators: (1) bile bacteria in different preoperative biliary drainage methods; (2) clinicopathological characteristics of patients with positive bile bacteria; (3) drug resistance of bile bacteria in different methods of preoperative biliary drainage. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed as absolute numbers or percen-tages, and comparison between groups was analyzed by the chi-square test. Bonferroni correction was used for pairwise comparison. The inspection level was 0.016 7 in the multiple comparison. Results:(1) Bile bacteria in different preoperative biliary drainage methods: of 317 patients, 116 cases were positive for bacterial culture, including 168 strains of 43 bacterial types. There were 46 strains from 36 patients without preoperative biliary drainage, 49 strains from 39 patients with preoperative PTCD and 73 strains from 41 patients with preoperative ERBD. ① The positive rate of bacteria for 317 patients was 36.59%(116/317). The positive rates of bacteria for patients without preoperative biliary drainage, patients with preoperative PTCD and patients with preoperative ERBD were 22.78%(36/158), 33.91%(39/115) and 93.18%(41/44). There was a significant difference in the positive rate of bacteria among the three groups ( χ2=74.066, P<0.05). There was no significant difference between patients with preoperative PTCD and patients without preoperative biliary drainage ( χ2=4.137, P>0.016 7), but there were significant differences between patients with pre-operative ERBD and patients without preoperative biliary drainage or patients with preoperative PTCD ( χ2=72.305, 44.718, P<0.016 7). ② The overall multiple bacterial rate was 36.21%(42/116). The multiple bacterial rates for patients without preoperative biliary drainage, patients with preoperative PTCD and patients with preoperative ERBD were 19.44%(7/36), 23.08%(9/39) and 63.41%(26/41). There was a significant difference in multiple bacterial rate among the three groups ( χ2=20.431, P<0.05). There was no significant difference between patients with PTCD and patients without preoperative biliary drainage ( χ2=0.147, P>0.016 7), but there were significant differences between patients with preoperative ERBD and patients without preoperative biliary drainage or patients with preoperative PTCD ( χ2=15.133, 13.215, P<0.016 7). ③ The overall prevalence rate of multi-drug resistant organism was 30.95%(52/168). The prevalence rates of multi-drug resistant organism for patients without preoperative biliary drainage, patients with preoperative PTCD and patients with preoperative ERBD group were 15.22%(7/46), 26.53%(13/49) and 43.84%(32/73). There was a significant difference in the prevalence rate of multi-drug resistant organism among the three groups ( χ2=11.447, P<0.05). There was no significant difference between patients with PTCD and patients without preoperative biliary drainage ( χ2=1.827, P>0.016 7). There was a significant difference between patients with preoperative ERBD and patients without preoperative biliary drainage ( χ2=10.497, P<0.016 7), but there was no significant difference between patients with preoperative ERBD and patients with preoperative PTCD ( χ2=3.772, P>0.016 7). (2) Clinicopatho-logical characteristics of patients with positive bile bacteria: age, the history of abdominal surgery, degree of jaundice and location of biliary obstruction of patients were not related to the positive rate of bacterial culture ( χ2=4.865, 1.423, 4.922, 0.030, P>0.05). (3) Drug resistance of bile bacteria in different methods of preoperative biliary drainage: for patients without preoperative biliary drainage, the drug resistance rate of Gram-positive bacteria to nitrofurantoin, linezolid and tigecycline was 0, and the drug resistance rate of Gram-negative bacteria to piperacillin/tazobactam, gentamicin, tobramycin, amikacin and imipenem was 0. For patients with PTCD, the drug resistance rate of Gram-positive bacteria to linezolid and tigecycline was 0. For patients with ERBD, the drug resistance rate of Gram-positive bacteria to linezolid and tigecycline was 0. In terms of Gram-positive bacteria, linezolid, tigecycline, vancomycin and nitrofurantoin were the top four antibiotics with the lowest resistance rate. In terms of Gram-negative bacteria, imipenem, piperacillin/tazobactam, amikacin and tobramycinn were the top four antibiotics with the lowest resistance rate. Seven strains of fungi showed no resistance to antifungal drugs. Conclusions:Patients with preoperative ERBD are more vulnerable to infectious complications, and more likely to form drug resistant organism and multi-drug resistant organism. For Gram-positive bacteria infection, linezolid, tigecycline and vancomycin can be used for treatment. For Gram-negative bacteria infection, imipenem, piperacillin/trzobactam, amikacin and tobramycin can be used for treatment.

Pathological study of the levator palpebrae superioris muscle in patients with different severities of simple congenital ptosis / 中华实验眼科杂志

Objective:To observe the pathological changes of levator palpebrae superiors muscle in patients with different severities of simple congenital ptosis (SCP).Methods:Levator palpebrae superiors muscle specimens from 102 eyes of 68 patients with SCP who received levator palpebrae superiors muscle shortening surgery at Wuhan Aier Hankou Eye Hospital from August 2018 to October 2019 were collected as the observation group.According to the severity of ptosis, the specimens were divided into three groups, coverage ≤4 mm group (n=35), coverage >4 mm to ≤6 mm group (n=30), and coverage >6 mm group (n=37). Fresh levator palpebrae superiors muscle tissues from 8 normal donors in Aier Eye Bank of Wuhan Red Cross were selected as the control group.All specimens were performed with Masson trichrome staining and immunohistochemical staining for α-smooth muscle actin (α-SMA), and ImageJ software was used to measure the collagen fiber area ratio, skeletal muscle fiber area ratio and the integrated absorbance (IA) value of α-SMA.Seventeen specimens (2 from the control group, 5 from coverage ≤4 mm group/coverage >4 mm to ≤6 mm group/coverage >6 mm group) were observed with a transmission electron microscope (TEM). This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Wuhan Aier Hankou Eye Hospital (No.HKAIER2018IRB-005-01). All patients and their legal guardians were well informed about the treatment method and the purpose of sampling and voluntarily signed informed consent.Results:Compared with the control group, the skeletal muscle fiber was reduced in number and was in disordered arrangement, and the striation of some muscle fibers disappeared, and hyperplastic fibrous connective tissue was found in intercellular substances in the observation group.The collagen fiber area ratio of the coverage ≤4 mm group, coverage >4 mm to ≤6 mm group, coverage >6 mm group were significantly higher than that of the control group, and the skeletal muscle fiber area ratio of the three groups was significantly lower than that of the control group (all at P<0.008 3). There were more smooth muscle fibers and positive expression of α-SMA found in the specimens of the observation group.The IA value of α-SMA of the coverage ≤4 mm group, coverage >4 mm to ≤6 mm group, coverage >6 mm group was 7 195.28(5 935.69, 14 058.29), 55 584.18(33 861.88, 80 419.32), 166 507.76(119 121.95, 187 890.86), respectively, which were all higher than 5 543.03(4 867.67, 8 312.02) of the control group, among which, there were statistically significant differences between the control group and the coverage >4 mm to ≤6 mm group, coverage >6 mm group (both at P<0.008 3). Abundant organelles and some damaged mitochondria were found in smooth muscle cytoplasm in the observation group with a TEM.But no characteristic structure of smooth muscle cells such as dense patch and dense body was detected.Conclusions:There are abnormal smooth muscle cells in the levator palpebrae superiors muscle of SCP patients, and the dysgenesis of the levator palpebrae superiors muscle may be related to this abnormal muscle cell.

Research progress of relevance between cholecystokinin and depression / 中国临床药理学与治疗学

Depression is a mental illness characterized by significant and lasting depression. Recent studies have found that cholecystokinin, as a small brain-gut peptide molecule, is widely distributed in the central nervous system and enteric nervous system. In order to further clarify the relationship between CCK and the pathogenesis of depression, this article reviews the effect of CCK in depression, including HPA axis, synaptic function and circuit mechanism, etc.

Detection and Clinical Significance of Thrombus Molecular Markers in Diffuse Large B-cell Lymphoma / 肿瘤防治研究

Objective To investigate the detection and clinical significance of thrombus molecular markers in diffuse large B-cell lymphoma (DLBCL). Methods We collected the blood specimens of 60 patients with DLBCL, involving 23 cases in the initial treatment group, 24 cases in the remission group and 13 cases in the non-remission group, 23 cases in the thrombus group and 37 cases in the non-thrombus group. We selected 46 healthy people in the same period as the control group. The levels of thrombomodulin (TM), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and thrombin-antithrombin Ⅲ complex (TAT) in plasma were detected by chemical immunoassay, and the levels of lactate dehydrogenase (LDH) in serum was detected by automatic biochemical analyzer. We analyzed the differences of thrombus molecular markers among groups and prognostic factors. Results The levels of TM and PIC in plasma of lymphoma patients were higher than those in health control group (P < 0.05). The levels of TM and PIC in the initial treatment and non-remission groups were significantly higher than those in the remission group (P < 0.05). The levels of TM, PIC and TAT in thrombus group were higher than those in non-thrombus group (P < 0.05). TM and PIC levels in plasma were closely related to the prognosis of DLBCL patients. PIC was an independent prognostic factor (P < 0.001). TM and PIC levels were correlated with LDH prognostic indicators in lymphoma patients. Conclusion TM and PIC levels in plasma are significantly increased in DLBCL patients. They are expected to be the indicators for effectiveness and prognosis of DLBCL patients.

Immunodepletion with Hypoxemia: A Potential High Risk Subtype of Coronavirus Disease 2019

BackgroundThe outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia, and discuss the relationship between hypoxemia severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient. MethodsThis is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis. ResultsApart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia during the hospitalization, and the severity of hypoxemia was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died. ConclusionsWe discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis may be a high risk of fatal pneumonia.

Construction and application evaluation of the information network platform for neonatal disease screening in Hubei Province / 公共卫生与预防医学

Objective To use the neonatal disease screening information platform to evaluate the effectiveness of screening for neonatal diseases in Hubei Province. Methods A total of 74 214 live births in the area under the jurisdiction of the Hubei Newborn Disease Screening Center and the newborns screened in the manual registration of disease screening in 2018 were selected as the control group. In addition, A total of 55 952 cases of live births in the same jurisdiction area in 2019 and neonatal data recorded in the neonatal disease screening system were included in the experimental group. The comparisons of the neonatal phenylketonuria, primary screening rate of congenital hypothyroidism, rescreening diagnosis rate and follow-up treatment between the two groups were carried out. Results The overall screening rate, the primary screening rate and rescreening diagnosis rate of the congenital hypothyroidism in the experimental group were higher than those in the control group, and the differences were statistically significant (P0.05). Conclusion The application of information network-based neonatal disease screening platform greatly improved work efficiency, reduced errors, enhanced screening rate and disease follow-up management capabilities, and thereby improved the management level of neonatal disease screening work.

The choice of preoperative biliary drainage for malignant obstructive jaundice of distal bile duct / 中华肝胆外科杂志

Objective:In order to optimize the mode of biliary drainage, we compared the different drainage methods of preoperative biliary drainage in the treatment of malignant obstructive jaundice of distal bile duct.Methods:From January 2015 to December 2018, 166 cases of distal biliary malignant obstructive jaundice treated by operation in the First Medical Center of PLA General Hospital were collected. According to the preoperative biliary drainage mode, 85 cases were divided into non drainage group, 56 cases in PTBD group and 25 cases in ERBD group; according to the operation mode, 116 cases were divided into radical pancreatoduodenectomy group and 50 cases were divided into palliative cholangiojejunostomy group, each group was divided into three groups according to the drainage mode. Chi square test and ANOVA were used to compare the results of bile bacterial culture and perioperative conditions of each group.Results:The positive rate of bile bacteria culture in non drainage group, PTBD group and ERBD group is 22.4% (19/85), 28.6% (16/56) and 100% (25/25). The positive rate in ERBD group is higher than that in PTBD group and non drainage group, the difference is statistically significant ( P<0.05). The proportion of multiple bacteria in ERBD group is higher than that in PTBD group and non drainage Group [64.0% (16/25) vs. 12.5% (2/16) vs. 5.3% (1/19)], the difference is statistically significant ( P<0.05). The proportion of common pathogens in ERBD group is higher than that in PTBD group and non drainage Group [97.8% (45/46) vs. 89.5% (17/19) vs. 66.7% (14/21)], the difference is statistically significant ( P<0.05). In pancreatoduodenectomy group, the operation time of ERBD group is significantly longer than that of PTBD group and non drainage group [(334.5±48.3) min vs. (289.4±39.5) min vs. (303.9±57.1) min], the difference is statistically significant ( P<0.05). The amount of bleeding in PTBD group is less than that in ERBD group and non drainage group [(268.8±128.4) ml vs. (388.2±181.6) ml vs. (366.1±220.4) ml], the difference is statistically significant ( P<0.05). There is no significant difference in the incidence of complications after pancreatoduodenectomy among three ways of drainage ( P>0.05). The incidence of clinically relevant postoperative pancreatic fistula is 6.8% (4/59), 10.0%(4/40) and 29.4%(5/17) in non drainage group, PTBD group and ERBD group. ERBD group is higher than non drainage group, the difference is statistically significant ( P<0.05). In palliative cholangiojejunostomy, there is no significant difference in operation time, amount of bleeding, postoperative hospital stay and complications among all groups ( P>0.05). Conclusion:Compared with ERBD, PTBD is a more suitable choice for patients who need preoperative biliary drainage before pancreatoduodenectomy.

Research progress in adiponectin and cognitive impairment / 中南大学学报(医学版)

Adipocytokines are polypeptides or proteins that are secreted by fat cells with a wide range of biological activities. Adiponectin is a fatty cytokine with insulin sensitization. It possesses the function of anti- diabetes, atherosclerosis and anti-inflammation. Adiponectin may participate in regulating the development of cognitive impairment, which is considered as a new regulatory factor for cognitive impairment.