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.

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.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

OBJECTIVE: To detect variants of IVD gene among 4 neonates with suspected isovalerate acidemia in order to provide a guidance for clinical treatment. METHODS: 111 986 newborns and 7461 hospitalized children with suspected metabolic disorders were screened for acyl carnitine by tandem mass spectrometry. Those showing a significant increase in serum isovaleryl carnitine (C5) were analyzed for urinary organic acid and variants of the IVD gene. RESULTS: Four cases of isovalerate acidemia were detected, which included 2 asymptomatic newborns (0.018‰, 2/111 986) and 2 children suspected for metabolic genetic diseases (0.268‰, 2/7461). The formers had no obvious clinical symptoms. Analysis of acyl carnitine has suggested a significant increase in C5, and urinary organic acid analysis has shown an increase in isovaleryl glycine and 3-hydroxyisovalerate. Laboratory tests of the two hospitalized children revealed high blood ammonia, hyperglycemia, decreased red blood cells, white blood cells, platelets and metabolic acidosis. The main clinical manifestations have included sweaty foot-like odor, feeding difficulty, confusion, drowsiness, and coma. Eight variants (5 types) were detected, which included c.158G>A (p.Arg53His), c.214G>A (p.Asp72Asn), c.548C>T (p.Ala183Val), c.757A>G (p.Thr253Ala) and 1208A>G (p.Tyr403Cys). Among these, c.548C>T and c.757A>G were unreported previously. None of the variants was detected by next generation sequencing of 2095 healthy newborns, and all variants were predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The incidence of isovalerate acidemia in Liuzhou area is quite high. Screening of metabolic genetic diseases is therefore recommended for newborns with abnormal metabolism. The discovery of novel variants has enriched the mutational spectrum of the IVD gene.
Infant, Newborn ; Child ; Humans ; Acidosis ; Carnitine ; Erythrocytes ; High-Throughput Nucleotide Sequencing

Objective:To identify and analyze different proteins expression in the periosteum of congenital pseudarthrosis of the tibia (CPT) using tandem mass tags (TMT) proteomics.Methods:The samples were divided into three groups, namely CPT with neurofibromatosis type 1 (NF1) group (NF1-CPT group), CPT without NF1 group (nonNF1-CPT group) and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 was regarded as the threshold to screen differentially expressed proteins (DEPs). Subsequently, bioinformatics resources such as online tools DAVID and STRING were used to conduct GO annotation, KEGG pathways enrichment and protein-protein interaction (PPI) network with DEPs. Results:A total of 347 proteins differentially expressed in NF1-CPT group, 212 of which were up-regulated and 135 down-regulated. We identified 467 DEPs in nonNF1-CPT group, including 281 up-regulated and 186 down-regulated. Among of them, NF1-CPT group and nonNF1-CPT group shared 231 DEPs, except for HLA-DRB1 which increased in NF1-CPT group but decreased in nonNF1-CPT group. The remaining 230 DEPs showed the same expression trend in the two positive groups, including 117 up-regulated and 113 down-regulated. In particular, a total of 116 proteins were altered only in NF1-CPT group, including 94 up-regulated and 22 down-regulated. However, there were 236 proteins altered only in nonNF1-CPT group, including 164 up-regulated and 72 down-regulated. The results indicated that the pathogenesis of NF1-CPT was similar as nonNF1-CPT largely with a few differences. Finally, compared with nonNF1-CPT, there were 47 proteins changed 1.5-fold and P-value <0.05 in NF1-CPT group. Conclusion:The proteins expression in the periosteum of CPT is different from that of normal tibia. The expression of periosteal protein is also different between NF1-CPT and nonNF1-CPT. The present study will deepen our understanding of the pathogenesis of CPT in the protein level.

Objective To determine ED50 and ED95 of oxycodone inhibiting responses to endotracheal intubation together with target concentration infusion of propofol.Methods ASA physical status Ⅰ or Ⅱ patients,aged 18-65 years,with body mass index 18.5-24.9 kg/m2,falling into Mallampati Score Ⅰ or Ⅱ,undergoing elective surgery under general anesthesia,were enrolled.Anesthesia was induced with intravenous injection of oxycodone,target concentration infusion of propofol with plasma concentration of 4μg/ml and intravenous injection of rocuronium 0.9 mg/kg when BIS＜60.The patients were endotracheally intubated and mechanically ventilated.The initial dose of oxycodone was 0.2 mg/kg.The dose of oxycodone was increased/decreased by ratio of 1.1 in the next patient by modified Dixon's up-and-down method.The response to endotracheal intubation was defined as an increase in the maximum mean arterial pressure and/or the maxmium heart rate≥20％ of the baseline value with 2 minute after intubatior.Probit analysis was used for calculating ED50,ED95 and 95％ confidence interval (CI) of oxycodone inhibiting responses to endotracheal intubation.Results There were twenty-seven patients who completed the test finally.ED50 and ED95 (95％ CI)of oxycodone inhibiting responses to endotracheal intubation were respectively 0.204 (0.175-0.249)mg/kg and 0.342(0.287-0.409) mg/kg.Conclusion When plasma target concentration of propofol 4 μg/ml is infused,ED50 and ED95 of oxycodone inhibiting responses to endotracheal intubation is 0.204 and 0.342 mg/kg,respectively.

Teaching competition is an effective way for college and university teachers to improve their teaching skills. Based on the teaching practice and experience in medical parasitology,this paper discusses several key issues in teaching competition including topics,teaching designs and teaching methods. It provides references for the teachers in department of parasitology of universities and colleges to improve the quality of classroom teaching.

Objective:To study the clinical efficacy of botulinum toxin type A injection in the treatment of upper facial dynamic wrinkles.Methods:A total of 35 patients with upper facial dynamic wrinkles treated in our hospital from February 2016 to October 2016 were selected as research objects.All the patients were treated with botulinum toxin type A.The excellence rate of 30min after treatment,3 d after treatment and 7 d after treatment were evaluated and compared.The facial wrinkles severity index of the patients were evaluated by the facial wrinkles scale (FWS),and the differences of the FWS index before treatment,4 weeks after treatment and 6 months after treatment were compared.The adverse reactions,like upper facial tension,fatigue and local injection of ecchymosis after treatment were observed and compared.Results:The excellence rate of the patients after treatment of 30 min,3 d and 7 d were gradually increased.The excellence rate of the patients after treatment of 3 d and 7 d were significantly higher than that of after treatment of 30 min,and the excellence rate of the patients after treatment of 7 d were significantly higher than that of after treatment of 3 d (P＜0.05).The FWS index of the patients after treatment of 4 weeks and 6 months were significantly lower than those of before treatment,and the FWS index of the patients after treatment of 4 weeks were significantly lower than that of 6 months after treatment(P＜0.05).After treatment,only 4 patients had slight discomfort and all of these symptoms were disappeared after 3-4 days,there was no effect on their normal work and life.Conclusion:Botulinum toxin type A injection has a remarkable clinical curative effect in the treatment of patients with upper facial dynamic wrinkles,can maintain tor a long time,and also has good safety,it is worthy clinical application.

Objective:To investigate the curative effect of botulinum toxin type A combined with plastic operation of pouches on patients with eye skin relaxation and its impact on patients' satisfaction,and to provide reference for clinical application.Methods:A total of 60 patients with eye skin relaxation,who were treated in Baoji Central Hospital from June 2015 to June 2016,were selected as subjects and divided into control group (n=28) and treatment group (n=32) according to the patients' choices.The patients of control group were treated with plastic operation of pouches,while the patients of treatment group were treated with botulinum toxin type A combined with plastic operation of pouches.The two groups were followed up for 6 months.The improvement of crow's feet,the relief of pouches and the improvement of eye skin gloss of the patients after operation were observed and recorded.The incidence of complications were also observed.At the end of the follow-up,the satisfaction degrees of the patients were investigated with the self-made questionnaire.Results:After treatment,the improvement rate(100％) of crow's feet of the treatment group was significantly higher than that(60.71％) of the control group;the improvement rate (96.88％) of pouches of the treatment group was significantly higher than that (32.14％) of the control group;the improvement rate (87.50％) of eye skin gloss of the treatment group was significantly higher than that (53.57％) of the control group,and the differences were statistically significant (all P＜0.05).After treatment,there was no significant difference in the incidence of incision swelling,small amount of secretions and small hematoma between the two groups (P＞0.05),the operation eye swelling and incision bruises outer canthus in the control group were more than those in the treatment group (P＜0.05).The total satisfaction rate [93.75％ (30/32)] of the treatment group was significantly higher than that[67.86％ (19/28)] of the control group,the difference was statistically significant (P＜0.05).Conclusion:Botulinum toxin type A combined with plastic operation of pouches in the treatment of eye skin relaxation has a better efficacy and safety,which can significantly reduce the incidence of operation eye swelling and incision bruises outer canthus,and improve patients' satisfaction rate.It is worthy of clinical application.

Objective To explore the anti-tumor effect of 17XL strains of Plasmodium yoelii(P.y)infection on melanoma in mice. Methods B16F10 tumor cells were axillarilly injected into the right flank of 20 C57BL/6 mice to establish tumor-bearing mouse models. The next day,the mice were randomly divided into a P.y infection group and control group,10 mice each group. Each mouse of the P.y infection group was intraperitoneally injected with 1×106 red blood cells including 20% P.y infection red blood cells,and each one of the control group were intraperitoneally injected with 1×106 normal red blood cells of C57BL/6 mice. The time of tumor formation of the mice in the two groups was observed and the tumor volumes were measured. Results The time of tumor formation in the P.y infection group[(11.30 ± 0.21)d]was significantly later than that in the control group [(10.40 ± 0.22)d](P < 0.05). From the tumors could be accurately measured to the study end point,both the tumors of mice in the two groups were growing,and the tumor volumes of mice in the P.y infection group were significantly less than those in the control group at each time point(all P < 0.05). The growth rate of tumors in the P.y infection group[(71.10 ± 6.29)mm3/d]was significantly slower than that in the control group[(302.80 ± 49.94)mm3/d](P < 0.05),and the growth rates of tumors every day in the P.y infection group were significantly slower than those in the control group(all P < 0.05). Conclusion The P.y in-fection can delay the occurrence of tumor and inhibit the growth of melanoma.