First Nerve-Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR-II and Photoacoustic Bioimaging.

Nerve-related fluorophores generally locate in the visible or near-infrared region with shallow penetration depth and easy uptake by surrounding tissues. Prolonging the optical window promotes resolution by minimizing photoscattering and eliminating autofluorescence for NIR-II (second near infrared; 1000-1700 nm) and photoacoustic bioimaging. In addition, combination of the two could help in colocalization of targets at the 3D level. Catheter-based renal sympathetic denervation (RDN), an alternative treatment recently finishing its clinical evaluation for treating resistant hypertension, is highly dependent on experience and in urgent demand for in vivo guidance in locating the nerve over the renal artery. Here, an NIR-II and photoacoustic bioimaging system based on a dye-modified anti-tyrosine-hydroxylase antibody (TH-ICGM) to illustrate the peritoneal sympathetic nerve-related region are combined. With high resolution (0.15 mm) in NIR-II region for both absorbance (λex = 925 nm) and fluorescence (bioimaging in λem ≥ 1300 nm), TH-ICGM succeeds in providing 3D coordinates of procedure position with a precision in 0.1 mm. As the first nerve-related NIR-II immunoprobe, TH-ICGM has great clinical potential as assistance for nerve-related interventions.

Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. Therefore, CR3022 has the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g., m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, indicating that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

Effect of psoralen on TopoIIα expression in breast cancer stem cells / 西安交通大学学报(医学版)

Objective To explore the effect of psoralen on topoisomerase IIα(TopoIIα) expression of breast cancer stem cells.Methods CD44+CD24-/low breast cancer stem cells were sorted from MCF-7/ADR by magnetic-activated cell sorting(MACS).We observed the growth characteristics of these stem cells through optical microscope and detected the growth-inhibitory effects of psoralen on breast cancer stem cells by CCK-8 assay and IC50 of adriamycin and adriamycin combined with psoralen to calculate the reversal index.The mRNA and protein expressions of Topo IIα were detected using RT-PCR and Western blot, respectively.Results Under the optical microscope, breast cancer stem cells presented spheres.IC10 and IC20 of psoralen on breast cancer stem cells were (6.77±0.23)μg/mL and (10.36±0.21)μg/mL.IC50 of adriamycin and adriamycin combined with psoralen on breast cancer stem cells was (90.03±3.56)μg/mL and (21.47±0.82)μg/mL, the reversal index was 4.19.Psoralen significantly raised the expressions of Topo Ⅱα at mRNA and protein levels.Conclusion Psoralen reversed the resistance of adriamycin by increasing the gene and protein expressions of breast cancer stem cells Topo Ⅱα and the drug targets.

Psoralen reverses glutathione-S-transferaseπ-mediated multidrug resistance in breast cancer stem cells / 中国组织工程研究

BACKGROUND:Breast cancer stem cells not only lead to theoccurrence of breast cancer, but also may cause breast cancer metastasis and recurrence. The relationship between stem cells and cell resistance is also gaining increasing attentions, and the focus on the stem cell treatment may result in unexpected results.OBJECTIVE:To explore the reversal effect of psoralen on glutathione-S-transferase π (GST-π) in human breast cancer MCF-7/ADR cells and its mechanism.METHODS:MCF-7/ADR cells were cultured and enriched in serum-free medium to obtain breast cancer stem cells.RT-PCR and western blot were used to detect the expression of GST-π at the levels of gene and protein in the MCF-7/ADR cells after treatment with 0, 4, 8, 12, 16 mg/L psoralen. To observe the activation of nuclear factor-κB,western blot was used. The expression of GST-π was detected by RT-PCR in 18 μmol/L SN50 group and 8 mg/L psoralen group. Cell counting kit-8 assay was used to detect the effect of doxorubicin on cell proliferation.RESULTS AND CONCLUSION:Compared with the control group, psoralen reduced the expression of GST-π at the mRNA and protein levels, and significantly inhibited the activation of nuclear factor-κB. It was suggested that psoralen could reverse the multidrug resistance of human breast cancer MCF-7/ADR stem cells by decreasing the expression level of GST-π. The mechanism may be achieved by inhibiting the nuclear factor-κB signal pathway.

Comparison between indocyanine green fluorescence imaging plus methylene blue and plus carbon nanoparticles suspension injection for sentinel lymph node biopsy in breast cancer patients / 实用医学杂志

Objective To investigate the differences between indocyanine green (ICG) fluorescence imaging plus methylene blue and plus Carbon Nanoparticles Suspension Injection for sentinel lymph node biopsy (SLNB)in breast cancer patients. Methods A total of 134 cases of early breast cancer patients performed SLNB from November 2013 to November 2016 were involved,of which 48 cases were performed with ICG fluorescence imaging plus methylene blue,and another 86 cases plus Carbon Nanoparticles Suspension Injection. Results There was no significant difference between ICG plus Methylene Blue group and ICG plus nano carbon group in terms of detection rate(P>0.05),detected numbers(P>0.05),sensitivity(P>0.05),accuracy(P>0.05)and false negative rate(P > 0.05). Age,and body mass index(BMI)exerted no influence on the detection rate and accuracy of SLNB in two groups(P>0.05). Conclusion ICG Fluorescence Imaging plus Methylene Blue showed similar detection rate , detected numbers , sensitivity , accuracy and false negative rate as it plus Carbon Nanoparticles Suspension Injection for SLNB in breast cancer patients ,and both of them can be performed easily and conveniently.

Tumor specific delivery and therapy mediate by integrin ß6-target immunoliposomes for ß6-siRNA in colon carcinoma.

Adjuvant chemotherapy does not achieve the desired therapeutic efficacy in colon cancer as a result of the deficient reaction. Gene therapy using small interfering RNAs (siRNAs) delivered by target delivering system represents a potent and specific strategy in tumor therapy. Integrinß6 is exclusively expressed in malignant colonic epithelia, associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, designing an efficient and targeted delivery system for ß6-siRNA could be a potential approach to improve therapeutic efficacy of colon cancer. Here, we designed the Integrinß6 target immunoliposomes for highly efficient and selective delivery of ß6-siRNA in colon cancer, which consequently resulted in greatly growth suppression, invasion and metastasis of colon cancer cells. Moreover, it was able to greatly inhibit the tumor growing in vivo.

Effect of overexpression of vascular cell adhesion molecule-1 on migration of murine mesenchymal stem cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of overexpression of vascular cell adhesion molecule-1(VCAM-1)on the migration in vitro of the murine mesenchymal stem cells(MSCs)and its possible mechanism. METHODS The migration ability of normal mouse MSC (C3) ,empty vector-transfected MSC(C3+N) and VCAM-1 transfected MSC(C3+VCAM-1)was assessed by Transwell culture system in vitro after incubation for 8 and 12 h,respectively. The fetal bovine serum (FBS) was used as the chemotactic agent to induce MSC migration. The transmigrated cells were detected with methylosaniliam chloride(crystal violet)as well as DAPI staining.Furthermore,the specific chemical inhibitors of mitogen-activation protein kinase (MAPK) pathway ( SB203580,PD98059 and JNK inhibitorⅡ)were added to the Transwell system for 12 h and the alteration of the MSC migration ability was evaluated. RESULTS After incubation with FBS for 8 and 12 h,the absolute migrated cell number(7467 ± 485 and 8795 ± 255)and migration rate〔(14.9 ± 1.0)% and(17.6 ± 0.5)%〕of MSC in C3+VCAM-1 group were significantly increased compared with C3 group〔2731±562 and 4779±224, (5.5 ± 1.1)%and(9.6 ± 0.4)%〕and C3+N group〔2539 ± 321 and 5645 ± 1080,(5.1 ± 0.6)%and(11.3 ± 1.1)%〕(P<0.05,P<0.01),but there was no significant difference between C3 and C3+N groups. Moreover,the MSC migration ability of C3+VCAM-1 group was partially suppressed by addition of JNK inhibitorⅡ. The transmigrated cell number(4843 ± 167)and migration rate〔(9.7 ± 0.3)%〕were decreased compared with those of C3+VCAM-1 group without JNK inhibitorⅡ(P<0.01). SB203580 and PD98059,as specific chemical inhibitors of MAPK pathway,had no effect on MSC migration. CONCLUSION VCAM-1 can enhance mouse MSC migration in vitro and th4e mechanism may be related to JNK/MAPK pathway activation.

Breast cancer stem cells and clinical application / 国际肿瘤学杂志

Breast cancer stem cells (BCSC)are a class of breast cancer cells that have the capacity of selfrenewal and can differentiate into different cell lineages. These cells, with the ability of high tumorigenesis, invasion and metastasis, play a important role in breast cancer metastasis, recurrence and treatment resistance. The treatments targeting on breast cancer stem cells are very important for improving the efficacy of clinical therapy.

Advance of abdominal compartment syndrome / 国际外科学杂志

This review is to provide an overview of current situation and advance of abdominal compartment syndrome. Progress has been made in diagnosis and therapy of abdominal compartment syndrome. At present patients who are diagnosed as abdominal compartment syndrome are associated with a high mortality rate. Therefove, it is important to diagnoze and treat the disease early. Surgical treatment of increased intraabdominal pressure leads in most instances to a rapid and profound correction of the physiological abnormalities. Operative treatment is the unique and effective approach of abdominal compartment syndrome.

Occult thyroid carcinoma:report of 34 cases / 中国普通外科杂志

ObjectiveTo investigate the diagnosis and treatment of occult thyroid carcinoma(OCT).MethodsRetrospective analysis on the clinical data of 34 cases of OCT was made. ResultsOnly 6 cases were preoperatively diagnosed as OCT. Total resection of the affected lobe and isthmus was performed on 16 cases with neck dissection in 14 cases. Subtotal thyroidectomy was performed on 18 cases. The occult cancer lesion was pathologically confirmed within ipsolateral lobe in all the 34 cases. Neck lymph node metastasis was found in 4 cases and local infiltration in 3 cases. The psammoma bodies in cancer lesion and adjacent normal gland were found in 15 cases. Thirty-one cases were followed up for an average of 9 years. One died of lung metastasis and two more of other unrelated diseases. Conclusion(1) The psammoma bodies in normal thyroid gland usually imply the existence of cancer. (2) Total thyroidectomy of a lobe or subtotal thyroidectomy was the therapy of choice. Local infiltration or neck lymph node metastasis necessitates additional neck dissection.

Effects of ulinastatin on the serum level of MIF in rats with acute necrotizing pancreatitis / 中国现代普通外科进展

Objective: To explore the effects of ulinastatin on the level of MIF in rats with acute necrotic pancreatitis. Method: 52 healthy Wister rats were randomly divided into three groups: normal control group(group C, 12), ANP group(group A, 20)and UTI group(group U, 20). Severe acute pancreatitis rat model in group A were induced by injection of 315 % sodium taurocholate through retrogradely common biliopancreatic ducts via papilla duodeni. After inducing the rat model of ANP through the way above, rats in group U were treated by ulinastatin through portal vein injection. Pancreas and duodenum were only flipped after opening abdominal cavity in group C. Then rats were killed at 3rd, 6th ,12th ,24th hour after operation respectively. Cut the belly open at once, and draw blood in postcava. The levels of serum MIF were determined with ELISA. Blood amylase was detected through biochemistry instrument. Resected pancreas tissues was scored according to the standard of Kusske. Result: Compared to the normal control group, the level of serum MIF , blood amylase and histopathological scores were significantly increased in ANP group, P

Serum sCD44s and sCD44v6 levels in breast cancer patients / 中国病理生理杂志

AIM: To explore the clinical significance of detecting sCD44s and sCD44v6 in breast carcinoma.METHODS: Levels of serum soluble CD44 standard (sCD44s) and CD44 variant 6(sCD44v6) were detected by ELISA in 38 cases of breast cancer, 15 cases of benign breast diseases and 40 normal controls. RESULTS:The serum levels of sCD44s and sCD44v6 were significantly higher in patients with breast cancer than those with benign disease or normal controls. The serum concentrations of sCD44s and sCD44v6 in patients with stage Ⅲ, Ⅳ were significantly higher than those in patients with stage Ⅰ, Ⅱ(P