Objective To investigate the effect of amygdalin(AD)on fracture healing in osteoporotic(OP)rats and its possible mechanism.Methods SD rats were randomly divided into sham group,model group,inhibitor group and low,medium,high dose experimental groups,12 rats in each group.The OP rat model was established by bilateral ovariectomy.After the model was successfully established,rats in low,medium and high dose experimental groups were intraperitoneally injected with 0.1,0.5 and 1.0 mg·kg-1 AD;the inhibitor group was intraperitoneally injected with 5.0 mg·kg-1 H-89[cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate response element binding protein(cAMP/PKA/CREB)pathway inhibitor]+1.0 mg·kg-1 AD;sham group and model group were intraperitoneally injected with the same amount of 0.9％NaCl,once a day for 90 days.Micro-computer tomography was applied to observe the microstructure of the epiphysis in rats;the biomechanical status of femur was evaluated by orthopedic biomechanical test;the contents of serum osteocalcin(OC),C-terminal telopeptides of type Ⅰ collagen(CTX-Ⅰ),bone morphogenetic protein 2(BMP-2)and cAMP were detected by enzyme-linked immunosorbent assay(ELISA);the level of oxidative stress products in rat serum was detected by kit;Western blot was used to detect the expression of alkaline phosphatase(ALP)and cAMP/PKA/CREB signaling pathway protein(p-PKA/PKA,p-CREB/CREB)in rat bone tissue.Results The bone mineral density of sham group,model group and low,medium,high dose experimental groups,inhibitor group were(251.54±15.41),(135.82±10.92),(173.57±12.65),(204.31±14.48),(235.62±11.37)and(187.83±13.64)mg·cm-3;the contents of cAMP were(0.85±0.06),(0.20±0.03),(0.34±0.07),(0.48±0.09),(0.81±0.12)and(0.57±0.06)μmol·L-1;the expression of p-PKA/PKA were 0.96±0.08,0.06±0.02,0.35±0.04,0.67±0.07,0.94±0.09 and 0.37±0.05;p-CREB/CREB protein were 0.92±0.12,0.04±0.01,0.28±0.03,0.59±0.06,0.91±0.10 and 0.29±0.04,respectively.There were significant differences in the above indexes between sham group and model group,between low,medium,high dose experimental groups and model group,between inhibitor group and high dose experimental group(all P＜0.05).Conclusion AD can reduce oxidative stress,promote fracture healing and alleviate OP symptoms in rats.The mechanism may be related to the activation of cAMP/PKA/CREB signaling pathway.

BACKGROUND:Salvianolic acid B can inhibit cell damage induced by H2O2,effectively remove excess reactive oxygen species,and exert antioxidant properties.It has been used in the treatment of many diseases.However,there are relatively few studies on the role and mechanism of salvianolic acid B in intervertebral disc degeneration. OBJECTIVE:To observe the effect and mechanism of salvianolic acid B on oxidative stress-induced intervertebral disc degeneration by using gelatin methacryloyl hydrogel as a carrier through the in vitro cell experiment and the in vivo animal experiment. METHODS:The gelatin methacryloyl hydrogel(drug-loaded hydrogel)loaded with salvianolic acid B was prepared.(1)In vitro cell experiment:The lumbar nucleus pulposus cells of adult SD rats were isolated and extracted,and passage 3 nucleus pulposus cells were selected and divided into groups:Group A was added complete medium.In group B,a complete medium containing H2O2 was added.Group C was inoculated on methylacrylylated gelatin hydrogel and added with a complete medium containing H2O2.Group D was inoculated on methyl acrylyl gelatin hydrogel loaded with salvianolic acid B and added into a complete medium containing H2O2.The E group was inoculated on the methylacrylyl gelatin hydrogel loaded with salvianolic acid B,and the complete medium containing H2O2 and the complete medium containing TLR4 signaling pathway inhibitor were added.Cell proliferation,oxidative stress,inflammatory response,gene expression of cell matrix-associated proteins and the protein expression of TLR4/nuclear factor-kB signaling pathway were detected.(2)Animal in vivo experiment:Sixty adult SD rats were randomly divided into normal group,acupuncture group,acupuncture + salvianolic acid group,acupuncture + hydrogel group and acupuncture + loading potion gel group,with 12 rats in each group.The last four groups were treated with acupuncture to establish models of intervertebral disc degeneration and then injected with normal saline,salvianolic acid B solution,non-drug loaded gel and drug-loaded gel in turn.Imaging examination and pathological observation were performed 4 weeks after surgery. RESULTS AND CONCLUSION:(1)In vitro cell experiment:Compared with group A,the cell proliferation was decreased;the oxidative stress reaction and inflammation reaction were enhanced;the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was increased in group B(P<0.05),and the synthesis of extracellular matrix(type Ⅱ collagen,proteoglycan)was decreased(P<0.05).The protein expression of the TLR4/nuclear factor-kB signaling pathway was increased(P<0.05).Compared with group B,the cell proliferation of groups D and E was increased,the oxidative stress response and inflammatory response were weakened,and the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was decreased(P<0.05),and the synthesis of extracellular matrix was increased(P<0.05).The protein expression of TLR4/nuclear factor-kB signaling pathway was decreased(P<0.05),and the effect was more significant in group E.(2)Animal in vivo experiment:4 weeks after surgery,intervertebral disc height index,index of MRI and pathological and histological grading of the intervertebral disc had improved significantly in the acupuncture+drug-loaded hydrogel group,and simply injecting hydrogel or salvianolic acid B solution can to a certain extent improve the intervertebral disc degeneration,but they are not as good as the injection of the drug-loaded hydrogel.(3)It is concluded that gelatin methacryloyl hydrogel loaded with salvianolic acid B can inhibit oxidative stress and inflammation in the degenerated intervertebral disc tissue,inhibit the degradation of extracellular matrix,and alleviate the process of intervertebral disc degeneration,which may be accomplished by inhibiting the TLR4/nuclear factor-kB signaling pathway.

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Objective To summarize the clinical experience and risk factors for acute kidney injury (AKI) in neonates undergoing congenital cardiac surgery and demonstrate whether neonatal AKI after cardiac surgery was independently related to perioperative short-term outcomes. Methods Medical records of neonates undergoing congenital heart surgery from January 2014 to September 2021 were retrospectively reviewed. The patients were divided into an AKI group and a non-AKI group according to whether the AKI occured after the surgery. Multivariate logistic analysis was performed to analyze the risk factors for postoperative AKI and the relationship between postoperative AKI and postoperative short-term outcomes. Results A total of 609 patients were included. There were 395 males and 214 females with an age at surgery of 1.0-28.0 d and weight of 1.9-4.8 kg. After cardiac surgery, 139 neonates developed AKI. Multivariate logistic analysis showed that less intraoperative urine output [OR=0.96, 95%CI (0.94, 0.99), P=0.005], more intraoperative infusion of red blood cells [OR=1.49, 95%CI (1.16, 1.91), P=0.002], longer intraoperative deep hypothermic circulatory arrest time [OR=1.02, 95%CI (1.00, 1.04), P=0.020], higher vasoactive-inotropic score [OR=1.03, 95%CI (1.01, 1.04), P<0.001] and elevated lactate (increasing by 5 mmol/L) [OR=2.90, 95%CI (1.76, 4.76), P<0.001] when transferred to ICU were independent risk factors for AKI. AKI was an independent risk factor for increased in-hospital mortality [OR=12.61, 95%CI (3.00, 37.48), P<0.001]. Conclusion Less intraoperative urine output, more intraoperative infusion of red blood cells, longer intraoperative deep hypothermic circulatory arrest time, higher vasoactive-inotropic score and elevated lactate when transferred to ICU are independent risk factors for AKI. Furthermore, AKI is an independent risk factor for perioperative death after cardiac surgery.

Ten compounds were isolated and purified from the dichloromethane extract of stems of Ephedra intermedia by various chromatographic methods. Based on the analysis of physicochemical properties and spectral data, the structures of the ten compounds were identified as 1-allyl-3,4-dimethoxy-benzene-5-O-β-D-glucopyranoside (1), lyoniresinol (2), secoisolariciresinol (3), 4,3′,4′-trihydroxy-3-methoxylignan-9,9′-diyldiacetate (4), dehydroconiferyl alcohol (5), isocubebin (6), balanophonin B (7), sesquipinsapol B (8), crataegifin A (9), 1-(2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)ethan-1-one (10). Compound 1 is a new compound, named as 1-allyl-3,4-dimethhoxy-benzene-5-O-β-D-glucopyranosyl, compounds 2-10 are lignans and isolated from this plant for the first time. Compound 3, 4, 8 possess potentially anti-asthmatic activities.

Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.

Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.

Objective:To review the clinical status based on the best evidence of drug administration in patients with dysphagia, systematically analyze the obstacle factors and promoting factors in the process of evidence transformation, and formulate reform strategies.Methods:Based on the evidence-based nursing research method and the guidance of the Ottawa Model of Research Use (OMRU), the review indicators were developed based on the best evidence. The current status of clinical practice behaviors of 223 patients and 75 nurses in the Neurology, Neurosurgery and Geriatric departments of the Affiliated Hospital of Jiangsu University were reviewed from July to December 2021.Based on the results of the review, qualitative interviews were conducted with 32 potential adopters, and content analysis was used to assess the barriers and contributing factors to the clinical translation of evidence in three aspects: evidence-based change, potential adopters and practice environment, so as to develop effective strategies.Results:Based on the 22 best evidence selected, the evidence-based team developed 25 review indicators to carry out clinical review, showing that the compliance rate of 16 indicators were less than 60%. By analyzing and summarizing the interview results of potential adopters, the main obstacles leading to the low compliance rate of nurses were analyzed as follows: evidence-based reform changed the traditional work mode, and the application of evidence was not convenient; at the level of potential adopters, nurses had poor knowledge and practice, heavy work burden, and low awareness of patients and caregivers; at the level of practice environment, there was lack of nursing norms and procedures for clinical transformation of evidence, and the channels of multi-disciplinary collaboration and communication were not smooth. The main promoting factors were the perfect supervision mechanism of evidence-based nursing projects, the evidence-based group had rich experience in evidence transformation, the management was willing to change, and the practitioners were good at innovation.Conclusions:There is still a large gap between the clinical practice and the best evidence of drug administration in patients with dysphagia. The promoting factors should be fully utilized to overcome the obstacles and implement improvements to promote the effective transformation of evidence into clinical practice.

Based on medical cases about ginger juice in A Clinical Guide with Case Histories （《临证指南医案》）， we found that YE Tianshi apply ginger juice into the medicine mainly take its function of warming stomach to stop nausea， acrid-moist to unblock the collaterals， dissolving phlegm to expel fluid retention. It is often used with Ganjiang （Zingiber officinale）， Fuzi （Cyperus rotundus） and other warm medicinals to warm the yang qi； with Banxia （Pinellia ternata）， Huanglian （Picrorhiza kurroa） and other bitter-acrid medicinals to clear dampness and heat； with Zhuli （Arundo donax）， Juhong （Citrus reticulata） and other phlegm-resolving medicinals to clear turbid phlegm. Compared with the whole ginger， ginger juice is soft and easy to be absorbed； it is acrid-moist and can unblock the collaterals with stronger power. At the same time， it can enhance the effect of dissolving phlegm to expel fluid retention. Ginger juice can improve the efficacy of the medicinals and broaden the scope of ginger's medicinal use.