Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Stringent Tests of Lorentz Invariance Violation from LHAASO Observations of GRB 221009A.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

[Clinical effect of modified anterolateral acromioplasty in rotator cuff repair under shoulder arthroscope].

Objective: To compare the clinical effect of modified anterolateral and traditional acromioplasty in arthroscopic rotator cuff repair. Methods: The clinical data of 92 patients with total rotator cuff tears admitted to the Department of Joint Surgery of Jinhua Central Hospital from January 2016 to December 2019 were retrospectively analyzed. Of the patients, 42 were male, 50 were female, with a mean age of (57.1±13.2) years. Among them, 42 patients underwent traditional acromioplasty during arthroscopic rotator cuff repair (traditional group), and 50 underwent modified anterolateral acromioplasty (modified group). The preoperative and postoperative shoulder function of the patients in the two groups were evaluated and compared by using the University of California Los Angeles (UCLA), the rating scale of the American Shoulder and Elbow Surgeons (ASES), and the constant Murley shoulder score scale. And the preoperative and postoperative pain of patients was evaluated with visual analog scale (VAS). The incidence of rotator cuff retears 12 months after operation was counted. Results: There was no statistically significant differences in general information such as gender, age, affected side and course of disease between the two groups before the surgery (all P<0.05). All patients were followed up for (12.9±1.1) months. There was no significant differences in the UCLA score (31.4±3.0 vs 32.0±2.5), ASES score (13.1±0.7 vs 13.3±0.6), Constant Murley shoulder score (92.1±6.6 vs 94.3±4.6) and VAS score (1.5±0.8 vs 1.2±1.1) between the traditional group and the modified group 12 months after the operation (all P>0.05). The preoperative CSA (36.0°±1.7°) in the traditional group did not differ significantly from that at 12 months postoperatively (35.5°±1.2°) (P=0.270); the postoperative CSA at 12 months (30.8°±2.5°) in the modified group was significantly smaller than that before the operation (36.5°±1.9°), and also was smaller than that in the traditional group 12 months after the operation (35.5°±1.2°) (both P<0.05). At 12 months after operation, the rate of rotator cuff tears in the traditional group and modified group was 16.7% (7/42) and 4.0% (2/50), respectively (P=0.045). Conclusions: Traditional and modified anterolateral acromioplasty in treating total rotator cuff tears using arthroscopic rotator cuff repair can significantly improve shoulder joint function. However, modified anterolateral acromioplasty significantly reduces the CSA value and decreases the incidence of rotator cuff re-tears.

[Clinical characteristics and prognosis analysis of pulmonary sarcomatoid carcinoma].

Objective: To summarize the clinical characteristics, treatment, and outcomes of patients with pulmonary sarcomatoid carcinoma (PSC) in order to improve clinicians' understanding of this disease. Methods: The clinical data of patients diagnosed with PSC in our hospital from January 1, 2015 to November 30, 2023 were retrospectively analyzed. According to whether radical resection was performed, the patients were divided into resectable group and unresectable group. The characteristics and treatments of PSC in different groups were compared. The survival curves were drawn by Kaplan-Meier method to compare the prognosis of different groups of patients. Results: A total of 43 PSC patients were included, including 32 males, with an average age of (62.79±9.59) years, and 31 smokers. Peripheral-type tumors were more common, with imaging showing predominantly solid soft tissue masses, and the maximum diameter of the tumor was more than 5 cm in 14 patients. Among the 23 patients who underwent NGS gene testing, the KRAS mutation rate was 43.5%, the TP53 mutation rate was 30.4%, and the MET mutation rate was 8.7%, all of which were MET-14 exon skipping mutations. PD-L1 expression was detected in 13 patients, 10 of whom showed high expression. The median overall survival (mOS) of the 43 patients with PSC was 24.6 months (13.0-52.7 months). Among them, 22 patients underwent radical lobectomy plus mediastinal lymph node dissection, 13 patients had postoperative recurrence, and 7 patients died during follow-up. The median disease-free survival (mDFS) was 12.3 months, the mOS was not achieved and the 1-year OS rate was 77.3 %. Twenty-one patients had unresectable locally advanced or advanced stage, and 15 patients died. The mDFS was 2.5 months, the mOS was 6.2 months, and the 1-year OS rate was 42.9 %. Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. Conclusions: PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

[Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors].

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

[Effects of ppk1 deletion on the drug susceptibility of uropathogenic Escherichia coli producing ESBLs].

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes blaTEM and blaCTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Extended Very-High-Energy Gamma-Ray Emission Surrounding PSR J0622+3749 Observed by LHAASO-KM2A.

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

Vascular control by infrarenal aortic cross-clamping in placenta accreta spectrum disorders: description of technique.

We describe a novel surgical technique in 31 women with histopathologically confirmed placenta accreta spectrum (PAS) disorders managed by a multidisciplinary team using a prophylactic infrarenal abdominal aortic cross-clamping technique during caesarean hysterectomy. We conclude that this new surgical procedure is a relatively safe technique to potentially control operative blood loss. Our work may stimulate others to develop protocols assessing this innovative technique to improve the surgical outcome of PAS disorders.

[Impact of health literacy on patient experience of outpatients in China and its mechanism].

OBJECTIVE: To understand the relationship between health literacy and patient experience of outpatients in China, and to explore its mechanism. METHODS: The conceptual framework was developed based on Andersen's behavioral model of health services use and health literacy skills framework. An online cross-sectional survey was conducted with snowball sampling method, while the health literacy was measured by self-designed patient health literacy scale, and the patient experience was measured by the Chinese patient experience questionnaire for ambulatory care developed by Peking Union Medical College. And a structural equation model was built to explore the relationship between them and test the mechanism of health literacy influencing patient experience. RESULTS: A total of 2 773 subjects were investigated. The average score of health literacy was (90.72±12.90) points, accounting for 78.89% of the full score, and the dimension of seeking social support had the lowest score. The average score of overall rating of patient experience was (3.71±0.74) points, and the scores of each dimension of patient experience were between 3.56 and 3.80. The model fit indices of structural equation model for overall rating of patient experience among the outpatients were χ2/df=9.29 (χ2=4 107.27, df=442), root mean square error of approximation (RMSEA)=0.055 (< 0.06), comparative fit index (CFI)=0.926 (>0.90), Tucker-Lewis index (TLI)=0.918 (>0.90), standardized root mean square residual (SRMR)=0.061 (< 0.08), the model was acceptable. The variance in patient experience explained by the model was 0.108. The structural equation model analysis results showed that the overall rating of outpatient experience was directly affected by health literacy (ß=0.263, P < 0.001), also indirectly affected by health literacy (ß=0.012, P < 0.001). In other words, the overall rating increased by 0.275 units for each standard deviation increase of health literacy. Self-evaluated health status mediated the relationship between health literacy and the overall rating of outpatient experience. In terms of diffe-rent dimensions of patient experience, the standardized path coefficient of the total effect of health literacy on patient experience was as follows: Information guidance 0.337, humanistic care 0.319, communication with doctors 0.294, service efficiency 0.240, and hospital environment 0.173. CONCLUSION: The patients with higher level of health literacy were more likely to have a better outpatient experience in China, and the information guidance experience and humanistic care experience were most affected by health literacy. And the communication and information utilization ability had the greatest influence on patient experience.

[Clinicopathological analysis of clear cell renal cell carcinoma with hemangioblastoma component].

Objective: To investigate the clinicopathological features, differential diagnosis and molecular characteristics of clear cell renal cell carcinoma (ccRCC) with hemangioblastoma component (ccRCC-HBc). Methods: Two ccRCC-HBc cases diagnosed at Fujian Provincial Hospital in September 2015 and March 2016, respectively, were included. Their morphological, immunohistochemical and molecular features were analyzed, including fluorescence in situ hybridization (FISH) detection of TFE3, TFEB and VHL genes. Related literature was reviewed to reveal the characteristics of this tumor. Results: The two cases occurred in 2 women, aged 33 and 66 years, respectively. The maximum diameters of the tumors were 4.0 cm and 8.5 cm, respectively. Histologically, the ccRCC component, representing approximate 10%-20% of the neoplasm, while the tumor cells arranged in flaky, nested, and solid distribution. The tumor cells had conspicuous nucleoli, with rich thin-wall capillary network in the stroma. The hemangioblastoma-like component, representing approximate 60%-70% of the neoplasm, showed a rich capillary network of single-layered flat endothelial cells enclosing stromal cells. The latter cell type showed a pale or eosinophilic cytoplasm exhibiting occasional lipid droplets. Rare cell nuclei appeared enlarged, pleomorphic, or bizarre. The two components were intermingled with each other. Immunohistochemically, the tumor cells were positive for PAX8, CKpan, EMA, vimentin, CD10, RCC, CAⅨ, and P504s in ccRCC area; in another area, the tumor cells were positive for α-inhibin, CD34 and vimentin, while CD10 were weakly positive. Neither TFE3 or TFEB gene split signal was detected in the 2 cases (0/2), nor was VHL gene mutation in case 2 (0/1). Conclusion: ccRCC-HBc is an extremely rare entity of ccRCC. The diagnosis is mainly based on clinical and pathological characteristics, as well as immunohistochemistry. Molecular pathology is helpful for its differential diagnosis. The primary approach of treating ccRCC-HBc is complete surgical excision and chemotherapy. The targeted treatment is helpful if possible.

Investigation of feather follicle morphogenesis and the expression of the Wnt/ß-catenin signaling pathway in yellow-feathered broiler chick embryos.

1. This study investigated the pattern of feather follicle morphogenesis and the expression of the Wnt/ß-catenin signalling pathway in the skin of yellow-feathered broiler chick embryos during feather development, using haematoxylin and eosin (H&E) staining and Western blot assays, respectively. 2. The results showed that the skin displayed protrusions during embryonic days E7-E9, feather buds elongated during E10-E11 with anterior-posterior and proximal-distal asymmetries, and the epidermis invaginated to form the primary feather follicles (Pfs) at E12. At E13, the formation of the feather follicle and the epidermis at the base of the feather bud further invaginated into the dermis. By E15, Pf formation was essentially complete, and secondary feather follicles (Sfs) appeared. It was speculated that Pfs and Sfs developed independently and that Pfs occurred earlier than Sfs. 3. Quantitative measurements of Pf density reached a maximum at E15 and then decreased gradually. Sf density started to increase from E15. 4. Protein expression levels of ß-catenin, TCF4, cyclin D1, and c-Myc were significantly increased during E8-E12 (P < 0.05) and then decreased from E13 to the day of hatching (DOH) (P < 0.05). The result of the ß-catenin immunolocalisation signal intensity assay was consistent with the result of the Western blot assay. 5. Collectively, the results indicated that the Wnt/ß-catenin signalling pathway is essential for promoting the development of feather follicles, especially during E7-E15.

[Esculin inhibits proliferation of triple negative breast cancer cells by down-regulating FBI-1].

Objective: To investigate the effect of esculin on the proliferation of triple negative breast cancer cells and its molecular mechanism. Methods: MDA-MB-231 cells were treated with 28, 56, 112, 225, 450 and 900 µmol/L of esculin for 24, 48 and 72 h, respectively, and the cell viability was detected by cell counting kit 8 (CCK-8) assay. In addition, MDA-MB-231 cells were treated with 0, 225, 450 and 900 µmol/L of esculin for 48 h. And then the changes in cell morphology were observed by inverted microscope. The clone-forming ability was detected by colony formation assay. The mRNA expression levels of FBI-1, p53 and p21 were detected using real-time fluorescence quantitative polymerase chain reaction. The protein expression levels of FBI-1, p53, p21 and Ki67 were detected by western blot. Results: Compared with the blank control group, the cell viability of MDA-MB-231 cells that treated with esculin significantly decreased in a dose-dependent and time-dependent manners. After treatment with esculin, MDA-MB-231 cells shrunk, flattened, adhered poorly to the culture dish and the cell spacing became larger. Meanwhile, shedding and incomplete cells appeared, of which 900 µmol/L of esculin treatment group showed the most dramatic changes. In addition, the colony formation ratios were decreased to (77.18±5.13)%, (65.94±4.98)% and (45.92±3.70)% in the 225, 450 and 900 µmol/L of esculin treatment groups compared with blank control, respectively (P<0.01). Furthermore, the mRNA and protein expressions of FBI-1 increased, while the levels of p53 and p21 mRNA and protein, as well as the protein expression of Ki67 decreased in a concentration-dependent manner (P<0.01). Conclusion: Esculin may regulate cell cycle-related p53-p21 pathway via FBI-1 mediated DNA replication, thus inhibit the proliferation of triple negative breast cancer cells.

[Protective effect and mechanism of Lactobacillus rhamnosus on immune checkpoint inhibitors related colitis in mice].

Objective: Modeling the immune-related adverse events (irAE) colitis in mice, and explore the protective effect and related mechanism of Lactobacillus rhamnosus GG (LGG) on irAE colitis. Methods: C57BL/6 mice were divided into dextran sodium sulfate (DSS) group (n=3), DSS+anti-programmed death receptor 1 (PD-1) group (n=4), DSS+anti-PD-1+anti-cytotoxic T lymphocyte associated protein 4 (CTLA-4) Group (n=4), DSS+anti-PD-1+anti-CTLA-4+LGG group (n=4), all were given corresponding drugs and probiotics intervention. The severity of colitis were assessed by weight loss, disease activity index (DAI), colon length, colon histopathological score. The inflammatory cytokines and T cell immunity of CD4+, CD8+, FoxP3+regulatory T cells (Treg), were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining respectively. Results: Compared to DSS group, the Day 9 weight [(87.40±1.79)% vs (94.57±0.53)%, P<0.05], colon length [(5.33±0.27)cm vs (6.63±0.12)cm, P<0.05] were lower, and DAI score(2.66±0.24 vs 0.89±0.48), colon histopathological score (12.50±1.04 vs 5.67±0.33), tumor necrosis factor-α (TNF-α) (6.73±1.68 vs 0.91±0.40) (P<0.05), as well CD8+T cells (156.80±8.84 vs 89.00±6.66) and FoxP3+Treg cells (103.80±2.66 vs 48.33±3.18) (P<0.05) were higher in DSS+anti-PD-1+anti-CTLA-4 group. Compared to DSS+anti-PD-1+anti-CTLA-4 group, the DAI score(1.83±0.17 vs 2.66±0.24), colonic histopathology score (8.75±0.63 vs 12.50±1.04), TNF-α level (1.32±0.18 vs 6.73±1.68) (P<0.05) were lower; and CD8+T cells(97.75±3.75 vs 156.80±8.84, P<0.01) level was lower with higher FoxP3+Treg cells (126.00±8.33 vs 103.80±2.66, P=0.046) in DSS+anti-PD-1+anti-CTLA-4+LGG group. Conclusion: DSS combined with anti-PD-1 and anti-CTLA-4 can successfully modeling the irAE colitis in mice, LGG can reduce irAE colitis severity by regulating Treg cells.

[Prediction of short-term prognosis of hepatocellular carcinoma after TACE surgery based on MRI texture analysis technology].

Objective: To explore the feasibility of short-term efficacy prognosis prediction model for HCC patients undergoing transcatheter arterial chemoembolization (TACE) based on MRI-based radiomics technique. Methods: A total of 123 patients with liver cancer who received TACE treatment in Lishui Central Hospital from June 2016 to July 2018 were retrospectively collected, including 90 males and 33 females, with an average age of 24-83 (58±10) years. All the patients were pathologically confirmed as hepatocellular carcinoma and underwent MRI scan before surgery.All patients were followed up 3-4 months after TACE, and further divided into training group (n=85, 42 of which were effective and 43 cases were ineffective) and the validation group (n=38, 19 of which were effective and 19 were ineffective) according to the modified response evaluation criteria in solid tumors (mRECIST). There was no statistical difference in the general information between the two groups of patients, which was comparable. Then, preoperative T(2)WI images were used for radiomics analysis, texture parameters were screened based on R language, and short-term efficacy prediction model of TACE for training group and verification group was constructed. Results: T(2)WI image analysis of each patient received 396 different texture parameters, and further used Lasso dimensionality reduction and 10 times cross-validation screening to obtain 5 characteristic texture parameters, specifically stdDeviation, ClusterProminence_angle135_offset4, Correlation_angle135_offset4, Inertia_angle135_offset4, InverseDifferenceMoment_angle45_offset4. According to the above five texture parameters and their corresponding coefficient values, the corresponding radiomics scores (Radscore) were calculated, and the prediction models of the training group and the verification group were further constructed.It was found that the area under the ROC curve of the training group was 0.812 (95%CI: 0.722-0.901), the sensitivity and specificity were 83.7% and 69.0%, respectively. The area under the ROC curve of the validation group was 0.801 (95%CI:0.654-0.947), and the sensitivity and specificity were 89.5% and 63.2%, respectively. Conclusion: The constructed TACE prediction model in the present study has high prediction accuracy, sensitivity and specificity.The short-term efficacy prognosis prediction model for HCC based on MRI is constructed, stable and reliable.

[Comparison of modeling effects of two different 7, 12-dimethylbenz[a] anthracene induced breast cancer models in tree shrew].

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion: Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.