Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg^-1） group， and low- and high-dose （8.4 and 33.6 g·kg^-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

OBJECTIVE: To evaluate the performance of recombinase-aided amplification (RAA) assay in detection of Clonorchis sinensis metacercariae in freshwater fish samples, so as to provide insights into standardization and field application of this assay. METHODS: Wild freshwater fish samples were collected in the rivers of administrative villages where C. sinensis-infected residents lived in Jiangyan District, Xinghua County and Taixing County of Taizhou City, Jiangsu Province from June to September 2022. Genomic DNA was extracted from six freshwater fish specimens (5 g each) containing 0, 1, 2, 4, 8 and 16 C. sinensis metacercariae for fluorescent RAA assay, and the diagnostic sensitivity was evaluated. Fluorescent RAA assay was performed with genomic DNA from C. sinensis, Metorchis orientalis, Haplorchis pumilio and Centrocestus formosanus metacercariae as templates to evaluate its cross-reactions. In addition, the detection of fluorescent RAA assay and direct compression method for C. sinensis metacercariae was compared in field-collected freshwater fish samples. RESULTS: Positive amplification was found in fresh-water fish specimens containing different numbers of C. sinensis metacercariae, and fluorescent RAA assay was effective to detect one C. sinensis metacercaria in 5 g freshwater fish specimens within 20 min. Fluorescent RAA assay tested negative for DNA from M. orientalis, H. pumilio and C. formosanus metacercariae. Fluorescent RAA assay and direct compression method showed 5.36% (93/1 735) and 2.88% (50/1 735) detection rates for C. sinensis metacercariae in 1 735 field-collected freshwater fish samples, with a statistically significant difference seen (χ² = 478.150, P < 0.001). There was a significant difference in the detection of C. sinensis metacercariae in different species of freshwater fish by both the direct compression method (χ² = 11.20, P < 0.05) and fluorescent RAA assay (χ² = 20.26, P < 0.001), and the detection of C. sinensis metacercariae was higher in Pseudorasbora parva than in other fish species by both the direct compression method and fluorescent RAA assay (both P values < 0.05). CONCLUSIONS Fluorescent RAA assay has a high sensitivity for detection of C. sinensis metacercariae in freshwater fish samples, and has no cross-reactions with M. orientalis, H. pumilio or C. formosanus metacercariae. Fluorescent RAA assay shows a higher accuracy for detection of C. sinensis infections in field-collected freshwater fish than the direct compression method.
Animals ; Clonorchis sinensis/genetics* ; Metacercariae/genetics* ; Recombinases ; Fresh Water ; Fishes ; DNA ; Fish Diseases/diagnosis*

Objective:To analyze the medication law of Traditional Chinese Medicine (TCM) patent compounds for Alzheimer disease (AD) by using data mining method.Methods:The TCM compounds for the treatment of AD in the patent database were screened, and the frequency, clustering and association analysis were carried out with the help of TCM inheritance calculation platform, SPSS Statistics 21.0 and SPSS Modeler 18.0 software. The medication law was analyzed.Results:A total of 220 patent compounds were included, involving 361 kinds of Chinese materia medica; the top 10 high-frequency drugs were Acori Tatarinowii Rhizoma, Polygalae Radix, Ginseng Radix et Rhizoma, Chuanxiong Rhizoma, Astragali Radix, Lycii Fructus, Poria, Rehmanniae Radix PraeparataAngelicae Sinensis Radix, Salviae Miltiorrhizae Radix et Rhizoma; the most frequently used drugs were drugs for tonifying deficiency and promoting blood circulation to remove blood stasis; most of their properties belonged to warm, mild and cold; the tastes were mainly sweet, bitter and pungent; the meridians belonged to the five internal organs. 16 items of association data (4 combinations of two items and 12 combinations of three items) were obtained by association rule analysis, and the strongest correlation group was " Acori Tatarinowii Rhizoma- Polygalae Radix" and " Acori Tatarinowii Rhizoma- Chuanxiong Rhizoma- Polygalae Radix". Cluster analysis showed four prescription combinations and three pairs of drug compatibility, including the addition and subtraction structure of Kaixin Powder, Zuogui Pill, Bazhen decoction and so on. Conclusion:The core treatment principle of TCM patent compound treatment of AD is regulating and tonifying the five internal organs to treat its root, resolving phlegm and removing blood stasis to treat the symptoms, which accords with the theoretical basis of TCM in the treatment of AD, and can provide reference for clinical practice and new drug research and development.

OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.

Objective To understand characteristics and research status of literatures related to surgical site infec-tion(SSI)in China.Methods Literatures about SSI published between January 2000 and March 2016 were retrieved from China National Knowledge Infrastructure(CNKI),VIP database,Vanfang Database,and China Biology Medi-cine(CBM)database. Bibliometric method was adopted to analyze external and internal characteristics of literatures. Results A total of 1036 articles in Chinese were included,40(3.86% ),189(18.24% ),and 807(77.90% )were published in 2000-2005,2006-2010,and the first quarter of 2011-2016 respectively. Articles were mainly pub-lishedinChineseJournalofNosocomiology(n= 226,21.81% ),ChineseJournalofInfectionControl(n= 53, 5.12% ),andChineseJournalofDisinfection(n= 27,2.61% ). The research fields included risk factors(n= 277, 26.74% ),infection rates (n= 261,25.19% ),antimicrobial application (n= 208,20.08% ),and pathogens (n=153,14.77% );the infection rates were higher in general surgery and neurosurgery,the main pathogens were Esch-erichiacoli,Staphylococcusaureus,and Pseudomonasaeruginosa,risk factors mainly included the types of incision, duration of surgery,diabetes,age,and body mass index.Conclusion In recent years,articles about SSI research in-creases significantly,research in etiology and epidemiology has gained substantial achievement,but in the interven-tion and economics is still weak,suggesting that SSI research in economics,risk management,and behavioral aspects should be strengthened.

Objective To analyze the effect of personalized care based on comprehensive evaluation on the recovery and quality of life in the elderly with shoulder injury.Methods A total of 146 patients with shoulder joint injury in our hospital were randomly divided into control group and observation group,with 73 cases per group,given routine nursing measures and personalized care based on comprehensive evaluation,respectively.And shoulder joint injury recovery and quality of life of two groups were analyzed.Results Compared with nursing before,daily life activities ability,physical activity,myodynamia scores of two groups were increased and the observation group was significantly higher than control group (P ＜ 0.05);The pain scores were decreased in varying degrees in both groups,and the observation group was significantly lower than the control group (P ＜ 0.05).After nursing intervention,social relations,psychology,physiology,environmental scores were increased in some extent,and the observation group was significantly higher than control group (P ＜ 0.05);Coordination and comprehensive care (CCC),authorization and the cooperation (EP),offeting special information (PSI) related to the patients,respect and support nursing (RSC) and offering basic information (PGI) scores were significantly higher than that in the control group (P ＜ 0.05).Conclusion Individualized nursing intervention based on comprehensive evaluation can effectively promote the recovery of senile shoulder joint injury,and improve patients quality of life,so it is of great significance in clinic.

Objective To analyze the effect of personalized care based on comprehensive evaluation on the recovery and quality of life in the elderly with shoulder injury.Methods A total of 146 patients with shoulder joint injury in our hospital were randomly divided into control group and observation group,with 73 cases per group,given routine nursing measures and personalized care based on comprehensive evaluation,respectively.And shoulder joint injury recovery and quality of life of two groups were analyzed.Results Compared with nursing before,daily life activities ability,physical activity,myodynamia scores of two groups were increased and the observation group was significantly higher than control group (P ＜ 0.05);The pain scores were decreased in varying degrees in both groups,and the observation group was significantly lower than the control group (P ＜ 0.05).After nursing intervention,social relations,psychology,physiology,environmental scores were increased in some extent,and the observation group was significantly higher than control group (P ＜ 0.05);Coordination and comprehensive care (CCC),authorization and the cooperation (EP),offeting special information (PSI) related to the patients,respect and support nursing (RSC) and offering basic information (PGI) scores were significantly higher than that in the control group (P ＜ 0.05).Conclusion Individualized nursing intervention based on comprehensive evaluation can effectively promote the recovery of senile shoulder joint injury,and improve patients quality of life,so it is of great significance in clinic.

Objective To evaluate the role of heparanase in endotoxemia-induced destruction of vascular endothelial glycocalyx in rats.Methods Forty-eight pathogen-free male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were randomly divided into 3 groups (n=16 each) using a random number table: control group (group C), lipopolysaccharide (LPS) group (group L) and LPS+ heparin group (group LH).Endotoxemia was induced by intravenous LPS 15 mg/kg in L and LH groups, and heparin sodium 100 U · kg-1 · h-1 was infused simultaneously in group LH.At 3 and 6 h after LPS injection, blood samples were collected from the femoral vein for determination of the serum concentrations of serum heparin sulfate (HS), syndecan-1, E-selectin and intercellular adhesion molecule-1 (ICAM-1) concentrations.The rats were then sacrificed, and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio).Results Compared with group C, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly increased in group L, and the serum HS and ICAM-1 concentrations were increased in group LH (P＜0.05).Compared with group L, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly decreased in group LH (P＜0.05).The pathological changes of lungs were obvious in group L, and were significantly mitigated in group LH.Conclusion Heparanase is involved in endotoxemiainduced destruction of vascular endothelial glycocalyx in rats.