Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Male , Female , Prospective Studies , Middle Aged , Biopsy/methods , Carcinoembryonic Antigen/blood , Treatment Outcome , Adult , Aged
The energy spread (ΔE) of an ion source is an important parameter in the production of a finely focused primary ion beam applied in secondary ion mass spectrometry (SIMS). A variable-focusing retarding field energy analyzer (RFEA) has been developed and tested with an Ar+ beam and an oxygen ion beam extracted from a 2.45 GHz microwave ion source, which is developed as a candidate ion source for SIMS applications. The simulation results show that the relative resolution ΔE/E of the designed RFEA reaches 7 × 10-5. The experimental results indicate that a focusing electrode can improve the ΔE measurement results, which is consistent with the simulation results. The ion energy distributions of the Ar+ beam and oxygen ion beam are of Gaussian distribution with the value of ΔE of 3.3 and 2.9 eV, respectively. These results indicate that the designed RFEA is reliable for measuring the ion beam energy spread. The developed RFEA is also used to study the plasma behavior in different settings, which reveals that plasma stability is critical to making a low energy spread ion beam. This paper will present the simulation, design, and test of the variable-focusing RFEA. Preliminary ion beam quality studies with this instrument will also be discussed.
A high brightness and low energy spread (∆E) ion source is essential to the production of a high-quality primary ion beam applied in secondary ion mass spectrometry (SIMS). A compact 13.56 MHz radio-frequency (RF) ion source with an external planar spiral antenna has been developed as a candidate ion source for the production of negative oxygen ion beams for SIMS application. This ion source is designed with a three-and-a-half-turn water-cooled planar antenna for RF power coupling, a multi-cusp magnetic field for effective plasma confinement, and a three-electrode extraction system. The experimental results show that more than 50 µA negative oxygen ion beams have been extracted, which consist of 56% O-, 25% O2-, and 19% O3-. The ion energy distribution of the negative oxygen ion beam exhibits a Gaussian distribution with a minimum ∆E of 6.3 eV. The brightness of the O- beam is estimated to be 82.4 A m-2 Sr-1 V-1. The simulation, design, and experimental study results of this RF ion source will be presented in this paper.
Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.
Neoadjuvant Therapy , Rectal Neoplasms , Female , Humans , Male , Biopsy, Needle , Chemoradiotherapy , Neoplasm Recurrence, Local/diagnosis , Prospective Studies , Rectal Neoplasms/surgery , Treatment Outcome , Adult , Middle Aged , Aged
The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.
The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.
Space charge effect of intense ion beam has critical influence on separation efficiency in the electromagnetic isotope separator. In this paper, a ribbon beam extraction system with slit electrodes for an electromagnetic isotope separator was designed and studied. The extracted beam currents were varied from 10 to 40 mA and the corresponding extracted beam energies were 40 keV and 100 keV respectively. The simulated output beam density distributions were used in the subsequent multi species particle transmission simulation with the space charge effect included. The separated isotope beam spot distributions at the focal plane were simulated under different space charge compensation factors and thus the optimum operation gas pressures in vacuum box were roughly estimated. For the case of high intensity and high power isotope beam collection, an isotope collector with a deceleration electrode was proposed to mitigate the effect of high power beam bombardment and the resultant temperature rising on the collector surface.
Objective: To analyze the characteristics of heart rate variability (HRV) in patients with vestibular migraine (VM) and to explore its possible mechanism. Methods: Forty-eight patients with VM [17 males and 31 females, age (36.2±9.2) years], 44 patients with migraine [15 males and 29 females, age (34.4±9.0) years], and 30 patients with health check-ups during the same period [12 males and 18 females, age (34.6±6.5) years old] were selected as study subjects. Ambulatory ECG monitoring was performed in all subjects, and the HRV characteristics of each group were analyzed from both daytime and nighttime time phases. Time domain parameters were analyzed: standard deviation of normal to normal (SDNN), root mean square of successive differences (RMSSD), and percentage of normal to normal intervals differing by more than 50 ms (pNN50). The parameters in the frequency domain were analyzed: high frequency power (HF), low frequency power (LF), and the ratio of low frequency to high frequency power (LF/HF). Statistical analysis of the data was performed using SPSS 26.0 software. Results: At night, RMSSD (F=6.694) and HF (F=9.434) were lower in the VM and migraine groups compared to the control group, while LF/HF (F=16.049) and LF (F=9.434) were elevated compared to the control group, with statistically significant differences (P<0.05 or P<0.01), while LF was significantly elevated in the VM group compared to the migraine group, with a statistically significant (P<0.05). On the daytime measurements, mainly LF was elevated in the vestibular migraine group compared with the control group, while RMSSD was decreased compared with the control group, with statistically significant differences (P<0.05). Conclusion: Autonomic dysfunction characterized by sympathetic hyperfunction and vagal hypofunction is present in VM patients and is more pronounced at night. In addition, the degree of autonomic dysfunction may be more pronounced in VM patients than in migraine patients.
Migraine Disorders , Vertigo , Adult , Female , Heart Rate/physiology , Humans , Male , Middle Aged
Alternative splicing (AS) regulates mRNAs at the post-transcriptional level to affect both their amounts and the protein function. However, little is known about the roles of AS in regulation of biosynthesis of amino acids, flavonoids, and volatile compounds in tea plants. In this study, we used Iso-seq and transcriptome deep sequencing (RNA-seq) to identify AS events, and analyzed the expression of respective mRNAs in tea plants under drought (DS), heat stress (HS), and their combination (HD). By RT-PCR, we validated the AS events in nine genes involved in the biosynthesis of amino acids and flavonoids. The genes accumulating AS transcripts under DS, HS, and HD conditions included those encoding for anthocyanidin reductase (ANR), dihydrofavonol-4-reductase-like (DFRA), and chalcone isomerase (CHI). Similarly, genes directly or indirectly involved in the biosynthesis of volatile compounds such as lipoxygenase (LOX), terpenoid/terpene synthase (TPS), and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) also had AS events. Our study revealed that AS might specifically regulate the biosynthesis of amino acids in tea plants under stressful conditions. Moreover, we suggest that the AS events within the ANR and DFRA transcripts might play an important role in the regulation of flavonoid biosynthesis under DS, HS, and HD conditions. This study improved our understanding of the genetic drivers of the changes in the content of bioactive ingredients of tea plants subjected to abiotic stresses.
Camellia sinensis , Droughts , Alternative Splicing , Amino Acids , Camellia sinensis/genetics , Flavonoids/metabolism , Gene Expression Regulation, Plant , Heat-Shock Response/genetics , Oxidoreductases/genetics , Plant Proteins/genetics , Tea/metabolism
Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.
A high-temperature oven based on the inductive heating technology was developed successfully at the Institute of Modern Physics in 2019. This oven features a durable operation temperature of over 2000 °C inside the tantalum susceptor. By carefully designing the oven structure, the material compatibility issue at high temperature has been successfully solved, which enables the production and routine operation of refractory metal ions with SECRAL-II (Superconducting Electron Cyclotron Resonance ion source with Advanced design in Lanzhou No. 2). To further apply this type of oven to the room temperature ECR ion sources LECR4 and LECR5 (Lanzhou Electron Cyclotron Resonance ion source No. 4 and 5), a mini-inductive heating oven has been fabricated and tested in 2020. By directly evaporating calcium oxide, some high charge state calcium beams have been produced successfully, such as 52 euA of 40Ca16+, 30 euA of 40Ca17+, and 12 euA of 40Ca18+. The detailed design and testing results will be presented and discussed.
OBJECTIVE: Pyroptosis can be seen in both physiological and pathological processes, and whether it plays a positive or negative role has not been fully clarified, especially in the study of cardiology, which deserves more attention. A model of cardiomyocyte Hypoxia/Reoxygenation was established to detect MicroRNA (miRNA) expression. MATERIALS AND METHODS: The C57BL/6 mice and H9c2 cells were respectively treated with Ischemic/Reperfusion (I/R) and Hypoxia/Reoxygenation (H/R). Then, the concentrations of interleukin-1ß (IL-1ß) and IL-18 were detected in serum and culture medium supernatant, as well as the expression levels of FOXO3, Caspase1, and PIK3R1. RESULTS: In I/R group, the concentrations of IL-1ß and IL-18 in the supernatant of H9c2 cell culture solution were significantly higher compared with the control group. Consistent with the supernatant concentrations of IL-1ß and IL-18, IL-1ß, and IL-18 were also increased at a high level in I/R group at the transcriptional level. Furthermore, the in vitro experiments showed that FOXO3 and Caspase1 were significantly upregulated in myocardial cells with the treatment of I/R group compared to sham group. Concerning pyroptosis, the expression of PIK3R1 was dramatically decreased and the expression of miRNA-1 was significantly increased in H9c2 cells. CONCLUSIONS: MiRNA-1 promoted pyroptosis of cardiomyocytes and release of inflammatory factors by downregulating the expression level of PIK3R1.
Class Ia Phosphatidylinositol 3-Kinase/genetics , Down-Regulation , Forkhead Box Protein O3/metabolism , MicroRNAs/metabolism , Animals , Cell Hypoxia , Cells, Cultured , Class Ia Phosphatidylinositol 3-Kinase/metabolism , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Myocytes, Cardiac/metabolism , Pyroptosis , Rats
In order to diagnose the electron cyclotron resonance (ECR) plasma, a high-efficiency collimation system has been developed at the Institute of Modern Physics, and the bremsstrahlung spectra in the range of 10 keV-300 keV were measured on a third generation superconducting ECR ion source, SECRAL-II, with a CdTe detector. Used as a comparative index of the mean energy of the high energy electron population, the spectral temperature, Ts, is derived through a linear fitting of the spectra in a semi-logarithmic representation. The influences of some main source parameters, such as the neutral gas pressure, extraction voltage, microwave power, and bias disk voltage, on the high energy electrons are systemically investigated.
An isotope enrichment system for 39Ar has been developed at the Institute of Modern Physics, which is designed to increase the abundance of 39Ar in the incident sample gas. With intense Ar+ beams produced by a 2.45 GHz electron cyclotron resonance ion source and a high mass resolution spectrometer system, Ar isotopes are evidently separated on the target plane and selectively collected by an Al target. The separated Ar isotopes have been identified on the target plane, which is consistent with the simulations. According to the recent cross-checked results with atom trap trace analysis, a high enrichment factor of 39Ar has been successfully achieved. This paper will present the design and test results of this system.
A very compact permanent magnet 2.45 GHz electron cyclotron resonance ion source has been designed and developed for various purposes. The microwave power is coupled into the plasma chamber using the coaxial antenna instead of the waveguide, the magnetic field is produced by two NdFeB permanent magnet rings, and the diameter of the source body is only 10 cm. The beam current under different conditions was measured. A maximum of 5.8 mA H+/H2 +/H3 + mixed beam could be extracted from a 5.5 mm diameter extraction aperture.
The Space Environment Simulation and Research Infrastructure project, which uses various ion beams as irradiated materials in life science research, is being built at the Harbin Institute of Technology. A new room temperature electron cyclotron resonance ion source, the Lanzhou Electron Cyclotron Resonance Ion Source No. 5 (LECR5), has been designed and constructed. It is an intense, highly charged, heavy ion beam injector which generates ion beams from H to Bi, typically â¼50 eµA 209Bi32+. The LECR5 is designed to operate at microwave frequencies in the range of 14.5-18 GHz. The typical magnetic parameters are designed based on those optimized for SECRAL, which operates at 18 GHz. This paper presents the LECR5 ion source, its test bench, and the preliminary beam results.
LAPECR3 (Lanzhou All Permanent magnet Electron cyclotron Resonance ion source No. 3) had been developed as an ion injector of Heavy Ion Medical Machine (HIMM) accelerator facility since 2009. The first HIMM accelerator facility was built in Wuwei city in 2015, and the LAPCER3 ion source has delivered C5+ ion beam to HIMM for more than 1000 days in the past four years. In order to improve the performance of the LAPECR3 ion source for intense carbon beams production, continuous research and development work has been made. The recently developed LAPECR3 ion source together with the new low-energy beam transportation can provide better performance in terms of both beam intensity and quality. This paper will generally review the LAPECR3 ion source operation status for HIMM, and the recent improvement will be presented, especially the stable beams production of C4+ and C5+.
Carbon , Cyclotrons , Electrons , Heavy Ion Radiotherapy/instrumentation , Heavy Ions
According to the requirements of ion beams extracted from an electron cyclotron resonance ion source transverse phase space coupling research and the afterglow beam property effective measurement, a pepper pot type meter called PEMiL (Pepper Pot Emittance Meter in Lanzhou) has been designed, fabricated, and commissioned to obtain the emittance of high intensity highly charged heavy ion beams. The direct current beam emittance measurement results verify the coupling property caused by the semisolenoid field. This paper also describes the scheme of multiple exposure accumulation which was applied to measure the afterglow beam property, and the transverse phase space distribution of the oxygen afterglow beam which was measured for the first time is presented.
A Laser Ion Source (LIS) can produce high charge state and high intensity ion beams (â¼emA), especially, refractory metallic ion beams, which makes it a promising candidate as an ion source for heavy ion cancer therapy facilities and future accelerator complexes, where pulsed high intensity and high charged heavy ion beams are required. However, it is difficult for the LIS to obtain a long pulse width while ensuring high current intensity, thus limiting the application of the LIS. To solve the conflict, magnetic fields are proposed to confine the expansion of the laser produced plasma. With a solenoid along the normal direction to the target surface, the lateral adiabatic expansion of the laser ablation plasma is suppressed which extends the pulse width of the ion beam effectively. The characteristics of laser ablation plasma with solenoid field confinement will be presented and discussed in this paper.
HIAF (High Intensity heavy ion Accelerator Facility) is a new accelerator complex under construction at the Institute of Modern Physics. As the main injector of this project, the high-charge-state ECR ion source needs to provide intense uranium beams, such as 700 eµA of U35+. This requires the performance of metal ovens to be further improved so that the crucible can operate at an ultrahigh temperature for a long time without damage in a high magnetic field (>3 T). In order to meet these requirements, an inductive oven with special thermal shielding and support has been developed in the past two years. The off-line test result has shown that this oven can reach up to 2000 °C with â¼1.2 kW of heating power. After â¼5 days of continuous running on the SECRAL-II platform, the tantalum crucible survived. In this contribution, we will discuss the structure of this inductive oven and analyze the test results as well.
