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HER2-positive breast cancer is an aggressive subtype that accounts for 15-20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. Here, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%), had a poor response to current anti-HER2 dual-targeted therapies and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment.
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Strategies that fully convert available racemic substrates into valuable enantioenriched products are urgently needed in organic synthesis. Reported herein is the first parallel kinetic asymmetric transformation of racemic cyclohexadienones. Racemic cyclohexadienones are first diastereoselectively converted into a new pair of racemic transient dienol intermediates, which are then parallel protonated by chiral phosphoric acid to deliver two sets of hydroindole products bearing a quaternary stereocenter with generally excellent enantioselectivity.
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Objective: To investigate the safety and efficacy of piezosurgery in anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). Methods: 47 patients with complex CSM (cCSM) underwent ACDF surgery from 2014 to 2017. Among these patients, 26 underwent ACDF using piezosurgery (group A) and 21 underwent ACDF by using traditional tools such as high-speed air drill, bone curette, and Kerrison bone punch (group B). Average surgical time, intraoperative blood loss, surgical complications, preoperative and postoperative Japanese Orthopaedic Association (JOA) scores, and improvement rate were measured. Results: Average surgical time and intraoperative blood loss were significantly lower in group A than those in group B (P < 0.01). The incidences of surgical complications were 3.8% and 23.8% in the A and B groups (P < 0.05), respectively. There were no significant differences in JOA scores and improvement rates between data collection periods at preoperative, 3-day postoperative, and 1-year postoperative follow-ups (P > 0.05). Conclusion: For treating cCSM, both the piezosurgery and traditional tools led to significant neurological improvement. However, the piezosurgery was superior to the traditional tools in terms of surgical time, blood loss, and complication rate. Hence, piezosurgery was a safe and effective adjunct for ACDF treating cCSM.
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Bloodstream infection (BSI) caused by bacteria is highly pathogenic and lethal, and easily develops whole-body inflammatory state. Immediate identification of disease-causing bacteria can improve patient prognosis. Traditional testing methods are not only time-consuming, but such tests are limited to laboratories. Recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) holds great promise for rapid nucleic acid detection, but the uncapping operation after amplification easily contaminates laboratories. Therefore, the establishment of a more effective integrated isothermal amplification system has become an urgent problem to be solved. In this study, we designed and fabricated a hermetically sealed integrated isothermal amplification system. Combining with this system, a set of RPA-LFD assays for detecting S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI were established and evaluated. The whole process could be completed in less than 15 min and the results can be visualized by the naked eye. The developed RPA-LFD assays displayed a good sensitivity, and no cross-reactivity was observed in seven similar bacterial genera. The results obtained with 60 clinical samples indicated that the developed RPA-LFD assays had high specifcity and sensitivity for identifying S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI. In conclusion, our results showed that the developed RPA-LFD assay is an alternative to existing PCR-based methods for detection of S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI in primary hospitals.
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Narrowband photodetectors have wide application potential in high-resolution imaging and encrypted communication, due to their high-precision spectral resolution capability. In this work, we report a fast response, high spectral rejection ratio, and self-filtered ultranarrowband photodetector with a new mechanism, which introduces bulk recombination by doping Bi3+ and cooperates with surface recombination for further quenching photogenerated charges generated by short-wavelength-light excitation in perovskite single-crystal. A perovskite film focused on collecting charges is fabricated on the single crystal by a lattice-matched solution-processed epitaxial growth method. Due to the formation of PN heterojunctions, a narrowband photodetector in this mechanism has remarkable spectral selectivity and detection performance with an ultranarrow full width at half-maximum (FWHM) of 7.7 nm and a high spectral rejection ratio of 790, as well as a high specific detectivity up to 1.5 × 1010 Jones, a fast response speed with a rise time and fall time of â¼8 and 137 µs. The ultrafast and ultranarrow spectra response of self-filtered narrowband photodetector provides a new strategy in high-precision and high-resolution photoelectric detection.
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The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibodyâdrug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low breast cancer (433 female and one male) and integrated genomic, transcriptomic, proteomic, and metabolomic profiling data. In this cohort, HER2-low tumors are more distinguished from HER2-0 tumors in the hormone receptor-negative subgroup. Within HER2-low tumors, significant interpatient heterogeneity also exists in the hormone receptor-negative subgroup: basal-like tumors resemble HER2-0 disease, and non-basal-like HER2-low tumors mimic HER2-positive disease. These non-basal-like HER2-low tumors are enriched in the HER2-enriched subtype and the luminal androgen receptor subtype and feature PIK3CA mutation, FGFR4/PTK6/ERBB4 overexpression and lipid metabolism activation. Among hormone receptor-positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype.
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Neoplasias de la Mama , Femenino , Humanos , Masculino , Neoplasias de la Mama/genética , Pueblos del Este de Asia , Perfilación de la Expresión Génica , ProteómicaRESUMEN
OBJECTIVE: To explore curative effect of conservative treatment of supination-lateral rotation (SER) with type â ¢ and â £ ankle fracture by bone setting technique. METHODS: From January 2017 to December 2019, 64 patients diagnosed with SER with type â ¢ and â £ ankle fracture were treated with manipulative reduction and conservative treatment (manipulation group) and surgical treatment with open reduction and internal fixation (operation group), 32 patients in each group. In manipulation group, there were 17 males and 15 females, aged from 15 to 79 years old with an average of (51.42±13.68) years old;according to Lauge-Hansen classification, there were 8 patients with supination external rotation type â ¢ and 24 patients with type â £. In operation group, there were 13 males and 19 females, aged from 18 to 76 years old with an average of (47.36±15.02) years old;7 patients with type â ¢ and 25 patients with type â £. Displacement of ankle fracture was measured by Digimizer software, and compared before treatment, 3 and 12 months after treatment between two groups. Lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement were measured and compared between two groups. Mazur score was used to evaluate ankle joint function. RESULTS: All patients were followed up from 12 to 36 months with an average of (17.16±9.36) months. There were statistical differences in lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement in manipulation group before and after reduction(P<0.05). Compared with operation group, there were no statistically significant differences in lateral malleolus shift, lateral malleolus shift, lateral malleolus contraction shift(P>0.05), while there were statistically significant differences in lateral malleolus shift, posterior malleolus shift up and down (P<0.05). Mazur scores of ankle joint at 3 months after treatment in manipulation group and operation group were 68.84±13.08 and 82.53±7.31, respectively, and had statistical differences(P<0.05), while there was no difference in evaluation of clnical effect(P>0.05). There were no differences in Mazur score and evaluation of clnical effect between two groups at 12 months after treatment (P>0.05). CONCLUSION: Bone setting technique could effectively correct lateral displacement of medial malleolus, lateral displacement of medial malleolus, lateral displacement of lateral malleolus and lateral contraction displacement of lateral malleolus in supination lateral rotation type â ¢ and â £ ankle fracture, and has good long-term clinical effect, which could avoid operation for some patients and restore ankle function after fracture.
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Fracturas de Tobillo , Tratamiento Conservador , Femenino , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Fracturas de Tobillo/cirugía , Supinación , Peroné , Articulación del Tobillo/cirugíaRESUMEN
Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs). Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded. Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs (P < 0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group (P < 0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ. Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection.
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Parabens are widely present in aquatic environments and pose potential health risk. Although great progress has been made in the field of the photocatalytic degradation of parabens, the powerful Coulomb interactions between electrons and holes are the major limitations to photocatalytic performance. Hence, acid-induced tubular g-C3N4 (AcTCN) was prepared and applied for the removal of parabens from a real water environment. AcTCN not only increased the specific surface area and light absorption capacity, but also selectively generated 1O2 via an energy transfer-mediated oxygen activation pathway. The 1O2 yield of AcTCN was 11.8 times higher than that of g-C3N4. AcTCN exhibited remarkable removal efficiencies for parabens depending on the length of the alkyl group. Furthermore, the rate constants (k values) of parabens in ultrapure water were higher than those in tap and river water because of the presence of organic and inorganic species in real water environments. Two possible pathways for the photocatalytic degradation of parabens are proposed based on the identification of intermediates and theoretical calculations. In summary, this study offers theoretical support for the efficient enhancement of the photocatalytic performance of g-C3N4 for the removal of parabens in real water environments.
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BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE. METHODS: Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed. RESULTS: The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group. CONCLUSION: Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th) 2 and Th1 cytokines.
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Antirreumáticos , Lupus Eritematoso Sistémico , Recién Nacido , Humanos , Femenino , Embarazo , Hidroxicloroquina , Resultado del Embarazo , Mujeres Embarazadas , Citocinas , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/tratamiento farmacológico , Aspirina/uso terapéuticoRESUMEN
Propylparaben (PrP) has attracted extensive concerns due to its wide occurrence in wastewater and potential health risk. Herein, nitrogen vacancy engineered reticulate g-C3N4 (Nv-RCN) was successfully synthesized for the photodegradation of PrP. Nv-RCN exhibited larger specific surface area, greater light absorption ability, higher transfer and separation efficiency of charge carriers in comparison with bulk g-C3N4 (CN). According to the characterization results and DFT calculation, nitrogen vacancy could capture electrons and facilitate oxygen adsorption. The Nv-RCN exhibited an outstanding PrP removal efficiency of 94.3 %, and the corresponding apparent rate constant of Nv-RCN was 3.37 times higher than that of CN. High O2 concentration (8 mg/L) and low pH value (pH = 3) promoted PrP photodegradation based on Box-Behnken Design. The O2- was the major radical during PCOP of Nv-RCN, and could oxidize PrP by decarbonylation and dealkylation. This study provided new insights to the improvement of photodegradation performance of g-C3N4 for parabens removal and related environmental remediation.
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Nitrógeno , Parabenos , Fotólisis , CatálisisRESUMEN
@#Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1 × 107IU/mL)and Remdesivir of the maximum concentration(150 μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC_(50))of human IFNα1b eye drops and human IFNα1b sprays were 29 958 and 37 550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.314 7,0.291 0 and0.300 3 μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.320 5,0.274 4 and 0.304 1 μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.
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OBJECTIVE: To observe the radiological change and curative effect of cervical spondylosis treated with cervical vertebra pulling therapy in young people. METHODS: A total of 65 patients(shedding in 5 patients and final inclusion in 60 patients) with cervical spondylosis who were treated from January 2018 to September 2019 were randomly divided into treatment group and control group according to the digital table method. There were 30 patients in treatment group, including 14 males and 18 females, aged from 20 to 44 years old with an average of(29.83±6.99) years, who were treated with cervical vertebra pulling therapy(once a week, 4 times in total). The control group consisted of 30 cases, 12 males and 18 females, aged from 18 to 43 years old with an average of (31.77±5.93) years, who received sitting traction therapy(once a week, 4 times in total). The changes of C2-C7 Cobb angle, arc-chord distance and T1 slope (T1S) in two groups were observed before treatment and 1 month after treatment, for intra-group and inter-group comparison;and the changes of numerical rating scale(NRS) in two groups were observed before treatment and 1, 3 months after treatment, for intra-group and inter-group comparison. RESULTS: Sixty patients were followed up for (3.2±0.3) months. There were no significant differences in NRS, C2-C7 Cobb angle, arc-chord distance and T1S between two groups before treatment (P>0.05). One month after treatment, the NRS, C2-C7 Cobb angle, arc-chord distance and T1S were(1.67±0.76) scores, (16.55±6.01)°, (10.95±4.04)mm, (18.95±4.19)° in treatment group and(1.40±0.86) scores, (10.23±5.94) °, (6.11±4.17) mm, (13.34±4.25)° in control group respectively. C2-C7 Cobb angle, arc-chord distance and T1S in treatment group were better than those in control group (P<0.05); there was no significant difference in NRS between two groups (P>0.05). Compared with before treatment, there were statistically significant differences in C2-C7 Cobb angle, arc-chord distance and T1S in treatment group(P<0.05), but no statistically significant differences in control group(P>0.05). Three months after operation, NRS of treatment group was (1.60±0.62) scores and that of control group was (4.17±0.70) scores. The treatment group was better than the control group(P<0.05). The scores of treatment group after treatment were lower than those before treatment(P<0.05), and there was no significant difference in control group before and after treatment(P>0.05). CONCLUSION: Cervical vertebra pulling method and cervical vertebra sitting traction can relieve the pain symptoms of patients with cervical spondylosis, but the effect of cervical vertebra pulling method is more durable;cervical vertebra pulling method can correct abnormal cervical sagittal parameters.
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Laminoplastia , Lordosis , Espondilosis , Adolescente , Adulto , Vértebras Cervicales/cirugía , Femenino , Humanos , Laminoplastia/métodos , Lordosis/cirugía , Masculino , Cuello , Estudios Retrospectivos , Espondilosis/cirugía , Adulto JovenRESUMEN
Background: To avoid unnecessary postoperative complications, it is essential to select breast cancer patients without axillary lymph node (LN) metastasis who might be eligible for exemption from sentinel lymph node biopsy (SLNB). However, the lymph node metastasis (LNM) of triple-negative breast cancer (TNBC) is difficult to predict if only considering clinical parameters. Hence, by investigating the difference between LN positive and LN negative patients, we aimed to build a multi-omics model able to better predict LNM in TNBC. Methods: A total of 445 TNBC patients with lymph node status and multi-omics data were enrolled and divided into training and validation sets. We analyzed both clinicopathological characteristics and multi-omics data to search for robust biomarkers, which were used to establish a multi-omics model. Results: Compared with LN negative patients, LN positive patients had an increasing number of mutational events, while the frequencies of both amplification and deletion in somatic copy number alterations (SCNAs) were lower in LN positive cases. After analyzing upregulated gene-related pathways, neutrophil-related pathways were found to be enriched in LN positive patients. Based on these omics analyses, 5 predictors were utilized to build a multi-omics model, and the area under the receiver operating characteristic curve was 0.790 in the training set and 0.807 in the validation set, showing a better performance than models using individual omics data. Conclusions: After analyzing the largest TNBC multi-omics cohorts, we identified the potential clinical and molecular characteristics that are related to LNM. A multi-omics model was developed and performed robustly in predicting LNM, with the potential assistance of tailoring unnecessary axillary LN management among TNBC patients.
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A novel family of inorganic-organic-hybrid SeFe3(CO)9-dipyridyl two- and one-dimensional Cu polymers was synthesized via the three-component liquid-assisted grinding (LAG) of [Cu(MeCN)4]+, inorganic cluster [SeFe3(CO)9]2- (1), and rigid conjugated dipyridyls 4,4'-dipyridyl (dpy) and 1,2-bis(4-pyridyl)ethylene (bpee) or flexible conjugation-interrupted dipyridyls 1,2-bis(4-pyridyl)ethane (bpea) and 1,3-bis(4-pyridyl)propane (bpp). They included a cluster-linked 2D polymer, [(µ4-Se)Fe3(CO)9Cu2(MeCN)(dpy)1.5]n (1-dpy-2D), a cluster-pendant 1D chain, [(µ3-Se)Fe3(CO)9Cu2(dpy)3]n (1-dpy-1D), cluster-blocked 1D polymers, [(µ3-Se)Fe3(CO)9Cu2(L)]n (1-L-1D, L = bpee, bpea), and a cluster-linked 2D polymer, [(µ4-Se)Fe3(CO)9Cu2(bpp)2]n (1-bpp-2D). The reversible dimensionality transformations of these three types of polymers accompanied by the change in coordination modes of 1 were achieved by the LAG addition of 1/[Cu(MeCN)4]+ or dipyridyl ligands. These polymers were found to possess tunable low-energy gaps (1.49-1.72 eV) that increased in the order regarding their structural features: cluster-linked 1-dpy-2D and 1-bpp-2D, cluster-blocked 1-bpea-1D and 1-bpee-1D, and cluster-pendant 1-dpy-1D and [(µ3-Se)Fe3(CO)9Cu2(L)2.5]n (L = bpee, 1-bpee-2D; bpea, 1-bpea-2D), indicative of the importance of the participation of cluster 1. The measured electrical conductivities of 1-bpp-2D, 1-bpea-1D, and 1-dpy-1D were 3.13 × 10-7, 2.92 × 10-7, and 2.30 × 10-7 S·cm-1, respectively, which were parallel for the trend in their energy gaps, revealing semiconducting behaviors, supported by XPS, XANES, and DFT calculations. The surprising semiconductivity of the conjugation-interrupted bpp-linked 1-bpp-2D was mainly ascribed to electron transport via C-H···O(carbonyl) hydrogen bonds and aromatic C-H···π contacts within its closely packed 2D layers. Water-/light-stable polymers 1-bpp-2D, 1-bpea-2D, and 1-dpy-1D were also demonstrated to exhibit excellent pseudo-first-order photodegradation toward nitroaromatics and organic dyes, where cluster-linked polymer 1-bpp-2D performed the best, as predicted by its structural features and narrow energy gap.
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As more people are spending the majority of their daily lives indoors, indoor air quality has been acknowledged as an important factor influencing human health, with increasing research attention in recent decades. Indoor air pollutants (IAPs), such as volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs), can cause acute irritation and chronic diseases. Photocatalytic oxidation (PCO) technology is an efficient approach for eliminating IAPs. In this review, the development of PCO technology was explained and discussed to promote future development of PCO technology for IAP elimination. First, the health effects and the measured concentrations of typical VOCs and SVOCs in indoor environments worldwide were briefly introduced. Subsequently, the development and limitations of some typical photocatalytic reactors (including packed-bed reactors, monolithic reactors, optical fiber reactors, and microreactors) were summarized and compared. Then, the influences of operating parameters (including initial concentration of contaminants, relative humidity, space velocity, light source and intensity, catalyst support materials, and immobilization method) and the degradation pathways as well as intermediates of PCO technology were elucidated. Finally, the possible challenges and future development directions regarding PCO technology for IAP elimination were critically proposed and addressed.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Compuestos Orgánicos Volátiles , Contaminación del Aire Interior/análisis , Catálisis , Humanos , Oxidación-Reducción , TecnologíaRESUMEN
BACKGROUND: Neuroendocrine tumors (NETs) frequently occur in the gastrointestinal tract, lung, and pancreas, and the rectum and appendix are the sites with the highest incidence. Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract, including the stomach, intestine, appendix, colon, and rectum. The pathological changes and clinical symptoms of NETs are not specific, and therefore they are frequently misdiagnosed. AIM: To investigate the clinical symptoms, pathological characteristics, treatment, and prognosis of rectal neuroendocrine tumors (RNETs) by analyzing the clinical and pathological data of 132 RNET cases at our hospital. METHODS: All RNETs were graded according to Ki-67 positivity and mitotic events. The tumors were staged as clinical stages I, II, III, and IV according to infiltrative depth and tumor size. COX proportional hazard model was used to assess the main risk factors for survival. RESULTS: These 132 RNETs included 83 cases of G1, 21 cases of G2, and 28 cases of G3 (neuroendocrine carcinoma) disease. Immunohistochemical staining showed that 89.4% of RNETs were positive for synaptophysin and 39.4% positive for chromogranin A. There were 19, 85, 23, and 5 cases of clinical stages I, II, III, and IV, respectively. The median patient age was 52.96 years. The diameter of tumor, depth of invasion, and pathological grade were the main reference factors for the treatment of RNETs. The survival rates at 6, 12, 36, and 60 mo after operation were 98.5%, 94.6%, 90.2%, and 85.6%, respectively. Gender, tumor size, tumor grade, lymph node or distant organ metastasis, and radical resection were the main factors associated with prognosis of RNETs. Multivariate analysis showed that tumor size and grade were independent prognostic factors. CONCLUSION: The clinical symptoms of RNETs are not specific, and they are easy to misdiagnose. Surgery is the main treatment method. The grade and stage of RNETs are the main indices to evaluate prognosis.
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The treatment and prognosis of malignant tumors are closely related to the time when the tumors are diagnosed; the earlier the diagnosis of the tumor, the better the prognosis. However, most tumors are not detected in the early stages of screening and diagnosis. It is of great clinical significance to study the correlation between multiple pathogeneses of tumors and explore simple, safe, specific, and sensitive molecular indicators for early screening, diagnosis, and prognosis. The Septin 9 (SEPT9) gene has been found to be associated with a variety of human diseases, and it plays a role in the development of tumors. SEPT9 is a member of the conserved family of cytoskeletal GTPase, which consists of a P-loop-based GTP-binding domain flanked by a variable N-terminal region and a C-terminal region. SEPT9 is involved in many biological processes such as cytokinesis, polarization, vesicle trafficking, membrane reconstruction, deoxyribonucleic acid repair, cell migration, and apoptosis. Several studies have shown that SEPT9 may serve as a marker for early screening, diagnosis, and prognosis of some malignant tumors, and have the potential to become a new target for anti-cancer therapy. This article reviews the progress in research on the SEPT9 gene in early screening, diagnosis, and prognosis of tumors.
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Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g., ipilimumab and pembrolizumab) has been accelerated by a dramatic improvement of long-term survival in a small subset of patients compared to conventional chemotherapy, growing interesting research has focused on immunotherapy. However, majority of patients have not benefited from checkpoint therapies that only partially remove the inhibition of T cell functions. Insufficient systemic T cell responses, low immunogenicity and the immunosuppressive environment of tumors, create great challenges on therapeutic efficiency. Nanotechnology can integrate multiple functions within controlled size and shape, and has been explored as a unique avenue for the development of cancer immunotherapy. In this review, we mainly address how nanoengineered vaccines can induce robust T cell responses against tumors, as well as how nanomedicine can remodel the tumor immunosuppressive microenvironment to boost antitumor immune responses.