Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Wenyang Jieyu Prescription Regulates Hippocampal Neural Plasticity in Depressed Mice via NLRP3/Caspase-1/IL-1β Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg-1）， Jieyu prescription （12.03 g·kg-1）， WJP （16.71 g·kg-1）， and fluoxetine （2.6 mg·kg-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.

Wenyang Jieyu Prescription Regulates Hippocampal Neuron Apoptosis and Improves Synaptic Plasticity in Depressed Mice via BDNF/Akt/mTOR Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.

Establishment of pharmaceutical care pathway based on the problems related to chemotherapy / 中国药房

OBJECTIVE To design pharmaceutical care pathway for the problems related to chemotherapy， and to evaluate whether it contributes to the detection and intervention of drug-related problems （DRPs） in chemotherapy patients. METHODS The pharmaceutical care pathway table and flow charts were constructed and implemented by pharmaceutical care practice experience. The patients who were admitted to our hospital for chemotherapy before and after the implementation of the pharmaceutical care pathway were divided into control group （before the implementation，60 cases） and observation group （after the implementation，64 cases）， respectively； the relevant medical records of patients in the control group were extracted to evaluate DRPs， and pharmaceutical care of chemotherapy-related problems was performed for patients in observation group to extract DRPs. The basic condition， chemotherapy condition， DRPs classification and intervention status， adverse reactions induced by chemotherapy， PCNE classification of DRPs， occurrence time of DRPs， and drug classes related to DRPs were compared between 2 groups. RESULTS There was no statistical significance in the basic situation， chemotherapy regimen and chemotherapy drug category between the two groups （P＞0.05）. DRPs occurred in 46 and 37 patients in control group and observation group， respectively. In both groups， DRPs mainly occurred during chemotherapy， and mainly in the early stage of chemotherapy. Using the new pathway， the detection of DRPs significantly increased from 52.17% in the control group to 91.89% in the observation group （P＜0.05）. The successful intervention rate of DRPs was significantly increased from 32.61% in the control group to 72.97% in the observation group （P＜ 0.05）. The incidence of adverse drug reactions significantly decreased from 28.33% in the control group to 12.50% in the observation group（P＜0.05）. The main problem type of DRPs in the control group was treatment effectiveness， which mainly involved adjuvant antitumor drugs， mainly due to the use of adjuvant anti-tumor drugs for off-label prescribing； that of the observation group was treatment effectiveness and treatment safety， which mainly involved vomiting drugs， mainly due to insufficient medication to prevent nausea and vomiting caused by chemotherapy. CONCLUSIONS The implementation of the pathway helps clinical pharmacists to detect and intervene in DRPs among chemotherapy patients， and reduces the occurrence of chemotherapy-induced adverse reactions.

Effective Ingredients of Chinese Medicine in Prevention and Treatment of Osteoarthritis by Regulating Oxidative Stress： A Review / 中国实验方剂学杂志

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

LipoxinA4 protects sepsis-induced acute kidney injury via the TLR4/MyD88/NF-κB pathway / 安徽医科大学学报

Objective To study the protective effect of lipoxin A4(LXA4)against sepsis-induced acute kidney in-jury(SAKI)in rats and its effect on the expression of toll-like receptor 4(TLR4),myeloid differentiation factor88(MyD88),nuclear factor kappa B(NF-κB)in the kidney.Methods Forty male specific pathogen-free C57BL/6J mice were randomly divided into SAKI group,SAKI+LXA4 group,sham procedure group,sham procedure+LXA4 group.The mice in SAKI group and SAKI+LXA4 group were given cecum ligation and puncture(CLP)to establish SAKI animal models.The mice in SAKI+LXA4 group and sham procedure+LXA4 group were given LXA4(40 ng/kg)with intraperitoneal injection 30 mins after CLP.All mice were sacrificed at the 24th hour after CLP to collect serum,urine and kidney tissues.The enzyme linked immunosorbent assay(ELISA)was used to test the serum creat-inine(Scr),blood urea nitrogen(Bun),interleukin-1 β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM-1)levels of mice.The pathologi-cal changes were examined through hematoxylin-eosin(HE)staining and Periodic Acid-Schiff(PAS)staining.And the mRNA levels of TLR4,MyD88,NF-κB p65 were detected through real-time PCR(RT-PCR);the expression lev-els of TLR4,MyD88,NF-κB p65,phospho-NF-KB p65(p-NF-KB p65)were detected through immunohistochemistry(IHC)and Western blot assay.Results ELISA showed that the values of Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 in SAKI group were higher than those in SAKI+LXA4 group(P＜0.05),and there were no significant differences in Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 between sham procedure group and sham procedure+LXA4 group.HE and PAS staining showed that SAKI group had severer pathological changes than SAKI+LXA4 group in the kidney structure(P＜0.05),while pathological structures of the kidney were normal in sham proce-dure group and sham procedure+LXA4 group.RT-PCR showed that the mRNA levels of TLR4,MyD88,N F-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the mRNA levels of TLR4,MyD88,NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05);The results of IHC,Western blot assay were as follows:The expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05).Conclusion TLR4/MyD88/NF-KB pathway plays an important role in the occurrence and development of SAKI,and LXA4 may reduce SAKI by inhibiting TLR4/MyD88/NF-κB sig-naling pathway.

Study on application of modified anterior pelvic floor functional reconstruction operation in pelvic organ prolapse / 重庆医学

Objective To analyze the application value of modified anterior pelvic floor reconstruction operation in pelvic organ prolapse.Methods A retrospective analysis was adopted.A total of 141 patients with pelvic floor reconstruction surgery in the obstetrics and gynecology department of Chongqing Municipal Ma-ternal and Child Health Care Hospital from January 2020 to December 2021 were included.The patients were divided into the observation group(modified anterior pelvic floor reconstruction operation,n=78)and control group(classic anterior pelvic floor reconstruction operation,n=63)according to the operation methods.The perioperative indicators,pelvic organ prolapse quantitation(POP-Q)score before and after operation,objective cure rate after operation,recurrence situation and pelvic floor quality of life score before and after operation were compared between the two groups.Results There was no significant difference in the surgical time,bleeding volume,duration of antibacteriakl drug use,and length of hospital stay between the two groups(P＞0.05).The POP-Q scores after surgerynin the two groups were signbificantly increase compared with before operation,and the objective cure rate in postoperative 12 months in the observation group was significantly higher than that in the control group at 12 months after surgery(91％.0 vs.81.0％,P＜0.05).There was no recurrence in the observation group after one year follow-up,while there were two cases of recurrence in the control group.The scores of the pelvic floor distress inventory short form 20(PFDI-20),pelvic floor impact questionnake,short form 7(PFIQ-7),and pelvic organ prolapse/incontinence sexual function questionnaire-12(PISQ-12)in 1 month after surgery in the two groups had statisticallyu significant differences compared with those before surgery(P＜0.05).After one year of follow-up,the patient global impression of improvement(PGI-I)score in the observation group was significantly lower than that in the control group(P＜0.05).Con-clusion The modified anterior pelvic floor reconstruction operation can effectively improve the quality of life in the patients,moreover the patients are not easy to relapse,so which is a new type of operation worthy of promotion.

Study on the Distribution of Traditional Chinese Medicine Constitution in Pregnant Women with Iron Deficiency Anemia and Its Influencing Factors / 广州中医药大学学报

Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in pregnant women with iron deficiency anemia(IDA)and its related influencing factors,so as to provide a reference for the TCM prevention and treatment of IDA in pregnancy.Methods A total of 109 eligible patients with IDA during pregnancy were included in the study.The general data of pregnant women,the TCM constitution types and relevant laboratory indicators including serum ferritin(Fer),hemoglobin(Hb)and mean corpuscular volume(MCV)were collected.Statistical analyses were conducted on the distribution of TCM constitution types of IDA pregnant women and its related influencing factors as well as the pregnancy outcomes.Results(1)The 109 IDA pregnant women were predominated by biased constitution types,accounted for 60 cases(55.05％).The distribution of the constitution types of 109 IDA pregnant women was as follows:balanced constitution(49 cases,44.95％)>damp-heat constitution(13 cases,11.93％)>yang deficiency constitution(12 cases,11.01％)>yin deficiency constitution(11 cases,10.09％)>qi deficiency constitution(10 cases,9.17％)>qi stagnation constitution(9 cases,8.26％)>blood stasis constitution(3 cases,2.75％)>phlegm-damp constitution(2 cases,1.83％).(2)Comparison of Hb and MCV levels in IDA pregnant women with various constitution types showed no statistically significant differences(P>0.05),but Fer level in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution(P<0.01),and the probability of occurrence of amniotic opacity in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution and other biased constitution types(P<0.05).Conclusion Damp-heat constitution is the most common TCM constitution type in pregnant women with IDA,followed by yang deficiency constitution,yin deficiency constitution and qi deficiency constitution.The damp-heat constitution may be the susceptible constitution of pregnant women with IDA,and IDA pregnant women with damp-heat constitution have significantly higher Fer level than those with balanced constitution,and also have the higher probability of occurrence of amniotic opacity than those with balanced constitution and other biased constitution types.

Investigation on the Correlation Between Traditional Chinese Medicine Constitution and Pathogenic Factors in Patients with Ankylosing Spondylitis / 广州中医药大学学报

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway / 上海交通大学学报（医学版）

Objective·To investigate the effect of neferine(Nef)on renal tissues of diabetic nephropathy(DN)rats and its related mechanism.Methods·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin,and the successfully constructed rats were randomly divided into DN group,Nef(low,medium and high)dose groups and Nef high-dose+pathway antagonist(AMD3100)group,with 10 rats in each group.At the same time,10 common rats were selected as the normal group.The levels of fasting blood glucose(FBG),24 h urinary protein,serum glycosylated hemoglobin(HbA1c),serum creatinine(Scr),blood urea nitrogen(BUN)and renal index of rats in the six groups were measured.Hematoxylin-eosin(H-E)and Masson staining were used to observe the pathological changes of renal tissues.The content of malondialdehyde(MDA)in renal tissues was determined by thiobarbituric acid(TBA)method,and the activities of superoxide dismutase(SOD)and catalase(CAT)in renal tissues were determined by water soluble tetrazolium(WST-1)method and ammonium molybdate method,respectively.The mRNA and protein expressions of stromal cell-derived factor-1(SDF-1)and CXC chemokine receptor 4(CXCR4)in renal tissues were detected by quantitative real-time PCR(qPCR)and Western blotting,respectively.Rat renal tubular epithelium cells NRK-52E were induced by high glucose(30 mmol/L glucose)to establish DN cell model.The cells were divided into control group,high glucose(HG)group,HG+Nef(low,medium and high)dose(i.e.HG+Nef-L,M and H)group,and HG+Nef-H +AMD3100 group.SOD and CAT activities were detected by WST-1 method and ammonium molybdate method,respectively.MDA content was detected by TBA method.The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting,respectively.CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate,respecti-vely.Results·Compared with the DN group,the levels of FBG,24 h urinary protein,HbA1c,Scr,BUN,renal index and MDA content in Nef(low,medium and high)dose groups and Nef high-dose+AMD3100 group were decreased,the mRNA and protein expressions of SDF-1 and CXCR4 were increased,and the activities of SOD and CAT were increased(all P<0.05).The degree of pathological damage and fibrosis of renal tissues was reduced;all of the above changes were dose-dependent.AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats.Compared with the HG group,NRK-52E cell viability,SOD and CAT activities,and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L,M and H groups,while apoptosis rate and MDA content were decreased(all P<0.05).AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage.Conclusion·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway,playing a renal protective role.

Severity of loneliness and factors associated with social and emotional loneliness among the elderly in three districts in Shanghai / 复旦学报（医学版）

Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.

The implementation and evaluation of a modified full appointment mode for daytime chemotherapy safety / 复旦学报（医学版）

Objective To explore the operation effect of the improved full-appointment mode of ambulatory chemotherapy,so as to provide reference for further improving the treatment process.Methods The enhanced full-appointment mode had been implemented in Fudan University Shanghai Cancer Center outpatient information system,which seamlessly integrated daytime chemotherapy assessment with comprehensive information management,formulated precise rules for chemotherapy appointments,and ensured efficient integration of relevant data.A comparative analysis was conducted between the period after optimization(Jan to Sep 2022)and the corresponding period in the previous year(Jan to Sep 2021),considering factors such as patient waiting time,human involvement,patient safety during chemotherapy,as well as nurse and patient satisfaction.Results After optimization,the time spent by patients was reduced from 52.12(32.73-83.05)to 20.04(11.87-41.10)minutes,with statistically significant difference(z=-78.144,P＜0.001).Additionally,the time spent by patients before and after optimization was significantly different in the distribution of＜30 minutes,30-60 minutes,and＞60 minutes(χ2=5 958.455,P＜0.001).Previously,one nurse and 2-3 security personnel were required to schedule appointments in the daytime chemotherapy center,while after optimization,there was no longer a need for nurses to arrange appointment windows and the number of security personnel was reduced to one,thereby optimized human operations.It was observed that the number of cases involving chemotherapy infusion reactions decreased from 59 to 46 following optimization,and the number of patients requiring rescue observation reduced from four to one.Notably,no rescue events occurred during non-day shifts,thus enhanced patient safety during treatment hours outside regular working hours.Furthermore,there was a statistically significant improvement in both nurses'and patients'satisfaction levels before and after implementation of these optimizations(P＜0.05).Conclusion The modified full appointment mode reduced patient waiting time,optimized human resources utilization,enhanced patient safety during chemotherapy,and improved satisfaction levels among both nurses and patients.The implementation of the modified full appointment mode for daytime chemotherapy centers was beneficial to their overall operation.

Predictive Value of Serum C18∶1-Cer and LPC18∶0 Levels in Early Pregnancy Women for Gestational Diabetes Mellitus / 现代检验医学杂志

Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

Construction and clinical practice of vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics / 中国实用护理杂志

Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.

Clinical analysis of 10 neonates with primary segmental volvulus / 中国新生儿科杂志

Objective:To summarize the clinical features of primary segmental volvulus (PSV) in neonates.Methods:A retrospective analysis was conducted on the clinical data of neonates with PSV who were admitted to the Department of Neonatal Surgery, Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2014 to May 2023. The clinical manifestations, auxiliary examinations, treatment and prognosis of the neonates were summarized, and descriptive statistical analysis was performed on the collected data.Results:A total of 10 neonates with PSV were included, with a mean gestational age of (34.1±3.0) weeks and birth weight of (2 291±646) g. Eight cases had an onset age of 3 d or less, and 2 cases had an onset age of more than 3 d. Abdominal distension was observed as the main manifestation in all cases, while bilious vomiting occurred in seven cases and hematochezia in five cases. Imaging examinations mainly revealed low intestinal obstruction without specific manifestations. Laboratory tests showed metabolic acidosis and varing degrees of anaemia. Nine cases underwent diagnostic abdominal puncture, of which five had bloody ascites, two had clear ascites, one had bloody mixed with fecal-like ascites, and one had chylous ascites. All the cases underwent emergency exploratory laparotomy and segmental small bowel resections with either primary intestinal anastomosis or enterostomy. All cases were successfully cured and had been followed up to the age of 4 months to 9 years with good growth and development as normal children of the same age.Conclusions:Neonatal PSV is an independent abdominal emergency characterized by non-specific clinical manifestations and difficult preoperative diagnosis, but the overall prognosis is favorable after active surgical treatment.

Clinical application and complication analysis of umbilical arterial catheterization in premature infants / 中国新生儿科杂志

Objective:To study the clinical application and complications of umbilical arterial catheterization (UAC) in premature infants.Methods:From January 2021 to December 2022, premature infants with UAC successfully inserted in NICU of our hospital were enrolled. According to birth weight (BW), the infants were assigned into three groups: <1 000 g, 1 000~1 499 g and ≥1 500 g. The perinatal data, UAC usage, UAC-related complications and risk factors of UAC-related complications were retrospectively analyzed.Results:A total of 39 premature infants received UAC, with gestational age 29.3(27.3, 30.4) weeks and BW 1 100 (900, 1 310) g. The insertion length (IL) of UAC was calculated using the average value of two formulas: a, IL (cm) =4×BW (kg) +7; and b, IL(cm) =3×BW (kg)+9. The accuracy of tube end position was determined using chest/abdomen radiography. 30(76.9%) cases had accurate position, 6(15.4%) had higher position and 3(7.7%) had lower position. The proportion of appropriately positioned tube end in <1 000 g, 1 000~1 499 g and ≥1 500 g groups were 80.0%, 76.5% and 71.4%, respectively, without statistically significant differences ( P>0.05) .No significant differences existed among the three groups in UAC duration and UAC routinely removal rate ( P>0.05). 9 cases (23.1%) of UAC were removed for specific reasons, including 4 cases of arterial spasm, 2 cases of withdrawal of treatment, 1 case of tube end displacement, 1 case of abdominal distension and 1 case of death. 21 cases received 1 U/ml heparin (0.9%NaCl solution) 0.5~1 ml/h arterial infusion. 23.8% (5/21) had hypernatremia and the level of sodium became normal after reducing the concentration of NaCl solution. Arterial vasospasm occurred in 4 patients with skin color changes of one side of the lower extremities. After UAC removal, the skin color returned to normal. Conclusions:UAC is helpful and safe for preterm infants, however, its complications should be alerted to.

Impact of evodiamine on retinal injury in diabetic rats by regulating cyclic adenosine monophosphate/protein kinase A signaling pathway / 眼科新进展

Objective To investigate the effect of evodiamine(EVO)on retinal injury in diabetic rats by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway.Methods Totally 96 Sprague-Dawley rats(192 eyes)were divided into the negative control(NC)group,Model group,low-dose EVO(EVO-L)group,medium-dose EVO(EVO-M)group,high-dose EVO(EVO-H)group,calcium dobesilate(CD)group,SQ22536 group and EVO-H+SQ22536 group,with 12 rats in each group.Rats in the NC group were intraperitoneally injected with physiological saline instead of streptozotocin,and diabetic retinopathy models were established in all other groups.After successful mod-eling,the drug was administered once a day for 4 weeks.The blood glucose level of rats in each group was measured by blood glucose meter;HE staining was applied to detect the pathological changes of the retina of rats;TUNEL staining was adopted to detect the apoptosis of ganglion cells in the retina of rats;the levels of superoxide dismutase(SOD),malondial-dehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and cAMP in the retina of rats were detected;West-em blot was used to detect the protein expressions of Bcl-2 associated X protein(Bax),P53 and phosphorylated protein ki-nase A(p-PKA)in the retina of rats.Results Compared with the NC group,the pathological injury of the retina in the Model group was more serious;the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP and p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the Model group,the pathological injury of the retina was relieved,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions decreased,and the SOD,cAMP and p-PKA/PKA protein expression increased in the EVO-L group,EVO-M group,EVO-H group and CD group,with statistically significant differences(all P＜0.05).Compared with the Model group,the retinal tissue of the SQ22536 group was severely damaged,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP,p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the EVO-H group,the EVO-H+SQ22536 group showed more serious pathological injury of retinal tissue,increased blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions,and decreased SOD,cAMP and p-PKA/PKA protein expression,and the differences were statistically significant(all P＜0.05).Conclusion EVO may alleviate retinal injury in diabetic rats by activating the cAMP/PKA signaling pathway.

Multicenter retrospective investigation and analysis of the rationality of the application of human albumin in cardiac surgery during the perioperative period / 药物流行病学杂志

Objective To investigate the clinical application of perioperative human serum albumin(HSA)in cardiac surgery in multiple regions in China,and to evaluate the rationality of its clinical application in conjunction with the clinical guidelines,in order to provide a reference for promoting the rational application of HSA.Methods The medical records of patients who underwent cardiac surgery from April to June 2019 in eight hospitals across the country were retrospectively collected.The statistical information on patients'general information,the dosage,course of treatment,and cost of HSA,and the serum albumin level before and after medication was analyzed to evaluate the use of HSA.Relevant evaluation criteria were established,and the rationality of its medication was evaluated.Results Data from a total of 449 patients were included for analysis,the appropriate rate of medication was 81.1％.The course of medication was mostly＞2-5 days and the total amount of HSA was mostly 50-99 g.The main purpose of medicaiton were improving colloid osmotic pressure,reducing exudation to improve interstitial edema,postoperative volume expansion.Conclusion Clinical attention should be paid to ensure the rational application of HSA in cardiac surgery during the perioperative period and prevent the abuse of blood products.

Analysis and Correlation between Peripheral Adiponectin and CD4+T Cell Subsets in Patients with Acute Gouty Arthritis / 医学研究杂志

Objective To compare the difference of peripheral blood adiponectin and CD4+T cell subsets between patients with a-cute gouty arthritis and healthy controls,to explore the correlation between adiponectin and serum uric acid,disease activity,CT4+T cell subsets and some cytokines in patients with gout.Methods The clinical data(including general data,neutrophils,erythrocyte sedimen-tation rate,C-reactive protein,blood uric acid,CT4+T cell subsets and some cytokines)of acute gout group(n=90)and healthy con-trol group(n=72)were collected.The level of adiponectin in peripheral blood of two groups were detected,and the differences of adi-ponectin and CD4+T cell subsets between the two groups were compared;the correlation between adiponectin and clinical data was ana-lyzed.Results The levels of serum adiponectin in the acute gout group were significantly lower than those in the healthy control group(P＜0.001),and the levels of Th2,Thl7,Th17/Treg were significantly higher than those in the healthy control group(P＜0.05),while the levels of Treg and Th1/Th2 were significantly lower than those in the healthy control group(P＜0.05).In the acute gout group,adiponectin was negatively correlated with neutrophil,erythrocyte sedimentation rate and C-reactive proten(r=-0.244,P＜0.05;r=-0.311,P＜0.05;r=-0.506,P＜0.001),there was no correlation with serum uric acid.In acute gout group,adiponectin was posi-tively correlated with Th1 and Th1/Th2(r=0.252,P＜0.05;r=0.218,P＜0.05).In acute gout group,adiponectin in peripheral blood was positively correlated with interleukin-2(IL-2),interleukin-4(IL-4)and interleukin-10(IL-10)(r=0.323,P＜0.05;r=0.377,P＜0.05;r=0.359,P＜0.05).There was a negative correlation between interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)(r=-0.265,P＜0.05;r=-0.299,P＜0.05).Multiple linear regression analysis showed that adiponectin in the acute gout group was negatively correlated with erythrocyte sedimentation rate,C-reactive protein,IL-6 and TNF-α(BESR=-12.541,P=0.003;BCRP=-8.256,P=0.024;BIL-6=-15.907,P=0.037;BTNF-α=-79.770,P=0.040),but positively correlated with Th1(BTh1=2.959,P=0.006).Conclusion The levels of adiponectin in the peripheral blood of patients with acute gouty arthritis were decreased,the levels of Th2 and Th17 were increased,and the levels of Treg were decreased.The decrease of adi-ponectin was related to the immunological disorder and inflammation in the patients with acute gouty arthritis.

Effect of RhoC silencing on migration and invasion of oral squamous cell carcinoma / 中国病理生理杂志

AIM:To explore the expression of RhoC in oral squamous cell carcinoma(OSCC)and its effects on the malignant biological behavior of OSCC cells.METHODS:The UALCAN and K-M plotter databases,alongside tis-sue sample analyses,facilitated understanding RhoC expression in cancer and its links to clinicopathological traits.Two small interfering RNAs(RhoC-siRNA)were constructed according to the RhoC gene sequence.The mRNA and protein ex-pression levels of RhoC in OSCC cells were determined.The protein levels of FAK,p-FAK,MAPK,p-MAPK,matrix me-talloproteinase-2(MMP-2)and MMP-9 were also examined by Western blot.Furthermore,the invasion and migration of OSCC cells were analyzed by Transwell assay and scratch test.Finally,the pulmonary metastasis model of nude mice was established.RESULTS:The results of the databases showed that RhoC was highly expressed in OSCC tissues,which was closely related to pathological stage,pathological grade and lymph node metastasis,but not significantly related to the sur-vival rate of patients.Furthermore,compared with paracancer tissues,the mRNA and protein expression levels of RhoC were increased in OSCC tissues(P<0.01).Silencing of RhoC prominently reduced the migration and invasion of OSCC cells as well as the protein levels of p-FAK,p-MAPK,MMP2 and MMP9(P<0.05).The protein levels of MAPK and FAK were unchanged(P>0.05).The fluorescence intensity of the experimental group was significantly lower than that of the control group,and the results of HE staining showed that the number of lung nodules in the experimental group was sig-nificantly reduced(P<0.05).CONCLUSION:RhoC can effectively influence the migration and invasion of OSCC cells,and its potential mechanism may be related to FAK/MAPK/MMPs signaling pathway.