Survival outcomes in locally advanced dMMR rectal cancer: surgery plus adjunctive treatment vs. surgery alone.

BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.

Effects of deficient mismatch repair on the prognosis of patients with stage II and stage III colon cancer during different postoperative periods.

BACKGROUND: We evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy. METHODS: This retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods. RESULTS: The median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years. CONCLUSION: The benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.

Galvanic-coupled Trans-dural Data Transfer for High-bandwidth Intra-cortical Neural Sensing.

A digital-impulse galvanic coupling as a new high-speed trans-dural (from cortex to the skull) data transmission method has been presented in this paper. The proposed wireless telemetry replaces the tethered wires connected in between implants on the cortex and above the skull, allowing the brain implant to be "free-floating" for minimizing brain tissue damage. Such trans-dural wireless telemetry must have a wide channel bandwidth for high-speed data transfer and a small form factor for minimum invasiveness. To investigate the propagation property of the channel, a finite element model is developed and a channel characterization based on a liquid phantom and porcine tissue is performed. The results show that the trans-dural channel has a wide frequency response of up to 250 MHz. Propagation loss due to micro-motion and misalignments is also investigated in this work. The result indicates that the proposed transmission method is relatively insensitive to misalignment. It has approximately 1 dB extra loss when there is a horizontal misalignment of 1mm. A pulse-based transmitter ASIC and a miniature PCB module are designed and validated ex-vivo with a 10-mm thick porcine tissue. This work demonstrates a high-speed and miniature in-body galvanic-coupled pulse-based communication with a data rate up to 250 Mbps with an energy efficiency of 2 pJ/bit, and has a small module area of only 26 mm2.

Circulating Methylated SEPT9 DNA Analyses to Predict Recurrence Risk and Adjuvant Chemotherapy Benefit in Stage II to III Colorectal Cancer.

BACKGROUND We aimed to evaluate the ability of circulating cell-free methylated SETP9 DNA (mSEPT9) to identify recurrence and to determine its clinical utility in adjuvant chemotherapy (ACT) regimen decisions. MATERIAL AND METHODS This study enrolled 426 patients with stage II-III CRC who received radical resection between January 8, 2018, and November 30, 2020. The median follow-up duration was 15.8 months (range, 8.1-43.4 months). The primary endpoint was recurrence-free survival (RFS). A propensity score matching model was used to minimize potential confounding covariates and to confirm our findings. RESULTS In stage II-III CRC patients, postoperative (within 1 month after surgery) mSEPT9 positivity was significantly correlated with worse RFS (HR=6.21, P<0.001), and it remained the strongest independent predictor in multivariate Cox regression analysis (HR=5.83, P<0.001), which was significantly superior to CEA, CA19-9, and CA242. During disease surveillance, mSEPT9 positivity preceded radiographic recurrence by a median of 5.0 months. The postoperative mSEPT9-positive patients benefited more from CAPEOX compared to FOLFOX (HR=3.97, P=0.017), while for mSEPT9-negative patients, CAPEOX and FOLFOX resulted in similar RFS (HR=1.70, P=0.322). Furthermore, 3 months of CAPEOX was more effective than 3 and 6 months of FOLFOX (HR=4.40, P=0.065; HR=1.56, P=0.073, respectively). CONCLUSIONS Our results revealed that mSEPT9 detection after radical resection could identify minimal residual disease (MRD) and could predict a high risk of recurrence in patients with stage II-III CRC. Furthermore, we show pioneering work that mSEPT9 detection could be used to guide the selection of an adjuvant chemotherapy regimen to improve RFS.

An Energy-Efficient and High-Data-Rate IR-UWB Transmitter for Intracortical Neural Sensing Interfaces.

This paper presents an implantable impulse-radio ultra-wideband (IR-UWB) wireless telemetry system for intracortical neural sensing interfaces. A 3-dimensional (3-D) hybrid impulse modulation that comprises phase shift keying (PSK), pulse position modulation (PPM) and pulse amplitude modulation (PAM) is proposed to increase modulation order without significantly increasing the demodulation requirement, thus leading to a high data rate of 1.66 Gbps and an increased air-transmission range. Operating in 6 - 9 GHz UWB band, the presented transmitter (TX) supports the proposed hybrid modulation with a high energy efficiency of 5.8 pJ/bit and modulation quality (EVM< -21 dB). A low-noise injection-locked ring oscillator supports 8-PSK with a phase error of 2.6°. A calibration free delay generator realizes a 4-PPM with only 115 µW and avoids potential cross-modulation between PPM and PSK. A switch-cap power amplifier with an asynchronous pulse-shaping performs 4-PAM with high energy efficiency and linearity. The TX is implemented in 28 nm CMOS technology, occupying 0.155mm2 core area. The wireless module including a printed monopole antenna has a module area of only 1.05 cm2. The transmitter consumes in total 9.7 mW when transmitting -41.3 dBm/MHz output power. The wireless telemetry module has been validated ex-vivo with a 15-mm multi-layer porcine tissue, and achieves a communication (air) distance up to 15 cm, leading to at least 16× improvement in distance-moralized energy efficiency of 45 pJ/bit/meter compared to state-of-the-art.

An Implantable Neuromorphic Sensing System Featuring Near-sensor Computation and Send-on-Delta Transmission for Wireless Neural Sensing of Peripheral Nerves.

This paper presents a bio-inspired event-driven neuromorphic sensing system (NSS) capable of performing on-chip feature extraction and "send-on-delta" pulse-based transmission, targeting peripheral-nerve neural recording applications. The proposed NSS employs event-based sampling which, by leveraging the sparse nature of electroneurogram (ENG) signals, achieves a data compression ratio of >125×, while maintaining a low normalized RMS error of 4% after reconstruction. The proposed NSS consists of three sub-circuits. A clockless level-crossing (LC) ADC with background offset calibration has been employed to reduce the data rate, while maintaining a high signal to quantization noise ratio. A fully synthesized spiking neural network (SNN) extracts temporal features of compound action potential signals consumes only 13 µW. An event-driven pulse-based body channel communication (Pulse-BCC) with serialized address-event representation encoding (AER) schemes minimizes transmission energy and form factor. The prototype is fabricated in 40-nm CMOS occupying a 0.32-mm2 active area and consumes in total 28.2 µW and 50 µW power in feature extraction and full diagnosis mode, respectively. The presented NSS also extracts temporal features of compound action potential signals with 10-µs precision.

An Energy Efficient and Temperature Stable Digital FLL-based Wakeup Timer with Time-Domain Temperature Compensation.

This brief presents an on-chip digital intensive frequency-locked loop (DFLL)-based wakeup timer with a time-domain temperature compensation featuring a embedded temperature sensor. The proposed compensation exploits the deterministic temperature characteristics of two complementary resistors to stabilize the timer's operating frequency across the temperature by modulating the activation time window of the two resistors. As a result, it achieves a fine trimming step (± 1 ppm), allowing a small frequency error after trimming (<± 20 ppm). By reusing the DFLL structure, instead of employing a dedicated sensor, the temperature sensing operates in the background with negligible power (2 %) and hardware overhead (< 1 %). The chip is fabricated in 40 nm CMOS, resulting in 0.9 pJ/cycle energy efficiency while achieving 8 ppm/ºC from -40ºC to 80ºC.

A Spatially Diverse 2TX-3RX Galvanic-Coupled Transdural Telemetry for Tether-Less Distributed Brain-Computer Interfaces.

A near-field galvanic coupled transdural telemetry ASICs for intracortical brain-computer interfaces is presented. The proposed design features a two channels transmitter and three channels receiver (2TX-3RX) topology, which introduces spatial diversity to effectively mitigate misalignments (both lateral and rotational) between the brain and the skull and recovers the path loss by 13 dB when the RX is in the worst-case blind spot. This spatial diversity also allows the presented telemetry to support the spatial division multiplexing required for a high-capacity multi-implant distributed network. It achieves a signal-to-interference ratio of 12 dB, even with the adjacent interference node placed only 8 mm away from the desired link. While consuming only 0.33 mW for each channel, the presented RX achieves a wide bandwidth of 360 MHz and a low input referred noise of 13.21 nV/√Hz. The presented telemetry achieves a 270 Mbps data rate with a BER < 10-6 and an energy efficiency of 3.4 pJ/b and 3.7 pJ/b, respectively. The core footprint of the TX and RX modules is only 100 and 52 mm2, respectively, minimizing the invasiveness of the surgery. The proposed transdural telemetry system has been characterized ex-vivo with a 7-mm thick porcine tissue.

The effectiveness of mindfulness-based intervention for psychological distress and emotion regulation in college students with non-suicidal self-injury.

This study explored the effectiveness of a short-term mindfulness-based intervention (MBI) on psychological distress, mindfulness levels, emotion regulation, and impulsivity among college students with non-suicidal self-injury (NSSI). Participants completed four questionnaires, including the Five Facet Mindfulness Questionnaire, the Depression Anxiety Stress Scale, the Emotion Regulation Questionnaire, and the Brief Barratt Impulsivity Scale, and two behavioral tasks, including an emotion regulation task and a stop signal task (SST), at three time points. Compared with the healthy group, the NSSI group had a significantly greater level of psychological distress and a lower level of mindfulness. Compared with the NSSI control group and the healthy group, the NSSI MBI group had significantly increased mindfulness levels and decreased psychological distress after the intervention. In the NSSI MBI group, regardless of which emotion regulation strategy was adopted when viewing negative pictures, the intensity of negative emotions during the emotion regulation task was significantly reduced. Moreover, in the NSSI MBI group, the effectiveness of the MBI on the mindfulness level, stress level, and emotion regulation process was maintained at the follow-up. The present study provided empirical support that short-term MBI has the potential to help individuals with NSSI by enhancing their emotion regulation.

Artificial intelligence in the anterior segment of eye diseases.

Ophthalmology is a subject that highly depends on imaging examination. Artificial intelligence (AI) technology has great potential in medical imaging analysis, including image diagnosis, classification, grading, guiding treatment and evaluating prognosis. The combination of the two can realize mass screening of grass-roots eye health, making it possible to seek medical treatment in the mode of "first treatment at the grass-roots level, two-way referral, emergency and slow treatment, and linkage between the upper and lower levels". On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology, quite a lot of studies have confirmed that machine learning can assist in diagnosis, grading, providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases, ametropia, lens diseases, glaucoma, iris diseases, etc. This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases, the current limitations, and prospects for the future.

Mild cognitive impairment estimation based on functional near-infrared spectroscopy.

Patients with mild cognitive impairment (MCI) are at a high risk of developing future dementia. However, early identification and active intervention could potentially reduce its morbidity and the incidence of dementia. Functional near-infrared spectroscopy (fNIRS) has been proposed as a noninvasive modality for detecting oxygenation changes in the time-varying hemodynamics of the prefrontal cortex. This study sought to provide an effective method for detecting patients with MCI using fNIRS and the Wisconsin card sorting test (WCST) to evaluate changes in blood oxygenation. The results revealed that all groups with a lower mini-mental state examination grade had a higher increase in HHb concentration during a modified WCST (MCST). The increase in the change in oxygenated hemoglobin concentration in the stroke group was smaller than that in the normal group due to weak cerebrovascular reactivity.

An Event-Based Neural Compressive Telemetry With >11× Loss-Less Data Reduction for High-Bandwidth Intracortical Brain Computer Interfaces.

Intracortical brain-computer interfaces offer superior spatial and temporal resolutions, but face challenges as the increasing number of recording channels introduces high amounts of data to be transferred. This requires power-hungry data serialization and telemetry, leading to potential tissue damage risks. To address this challenge, this paper introduces an event-based neural compressive telemetry (NCT) consisting of 8 channel-rotating Δ-ADCs, an event-driven serializer supporting a proposed ternary address event representation protocol, and an event-based LVDS driver. Leveraging a high sparsity of extracellular spikes and high spatial correlation of the high-density recordings, the proposed NCT achieves a compression ratio of >11.4×, while consumes only 1 µW per channel, which is 127× more efficient than state of the art. The NCT well preserves the spike waveform fidelity, and has a low normalized RMS error <23% even with a spike amplitude down to only 31 µV.

Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

BACKGROUND: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0 cm accompanied with major PVTT. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). RESULTS: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). CONCLUSION: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Ultrasound-guided medial branch of the superior laryngeal nerve block to reduce peri-operative opioids dosage and accelerate patient recovery.

BACKGROUND: To explore whether the medial branch block of superior laryngeal nerve can reduce the stress response of patients undergoing intubation and further reduce the dosage of opioids. METHODS: 80 patients undergoing gynecological laparoscopic surgery were selected, and randomly divided into 4 groups. All patients in the experimental groups received bilateral internal branch of superior laryngeal nerve block and transversus abdominis plane block. But the dosage of sufentanil used for anesthesia induction in the group A, B, and C was 0.4, 0.2, and 0µg/kg, respectively. Group D do not underwent supralaryngeal nerve block and the dosage of sufentanil was 0.4µg/kg. The heart rate (HR) and mean arterial pressure(MAP) were recorded at the time of entering the operating room(T1), before intubation after induction(T2), immediately after intubation(T3), 5min after intubation(T4), before extubation(T5), immediately after extubation(T6), 5min after extubation(T7). We also recorded the stay time in the recovery room, the number of cases of postoperative sore throat, the number of cases of nausea and vomiting, the first intestinal exhaust time, the length of hospital stay after operation. RESULTS: The HR of group A, C and D at T3 was significantly higher than that at T2(P < 0.01), while the HR of group B had no significant change. The HR of group A, C and D at T4 was lower than that at T3(P < 0.01), while the HR of group B had no obvious change. The HR of group C and D at T3 was significantly higher than that at T1 (P < 0.01). The MAP of group A and D at T4 was significantly lower than that at T1 (P<0.001). The first postoperative intestinal exhaust time in group A, B and C was significantly shorter than that in group D. The length of hospital stay after operation in group B and C was shorter than that in group D. CONCLUSIONS: Ultrasound-guided superior laryngeal nerve block combined with 0.2µg/kg sufentanil can reduce the intubation reaction, have better hemodynamic stability, reduce the first postoperative intestinal exhaust time and postoperative hospital stay, thereby accelerating the postoperative recovery of patients.

Hot Cracking Behaviors of Mg-Zn-Er Alloys with Different Er Contents.

The hot cracking behaviors of Mg-5Zn-xEr (x = 0.83, 1.25, 2.5, 5 wt.%) alloys are investigated by optimized hot cracking experimental apparatus, optical microscope, and scanning electron microscope, such as contraction behaviors, feeding behaviors, and permeability characteristics. It is found that the solid phase fraction at hot crack initiation and within the freezing range both increased with increasing Er contents up to 2.5 wt.% and then decreased at 5 wt.% Er content. The Mg-5Zn-5Er alloy exhibits the lowest solid phase fraction (87.4%) and a reduced freezing range (74.2 °C), which leads to more effective liquid feeding in the latter stages of solidification. Combined with the grain size, the permeability of the mushy zone, and fracture morphology, the overall permeability is optimal in the Mg-5Zn-5Er alloy, which is beneficial for feeding the cavities and micro-pores. Meanwhile, a large amount of W phase precipitated by the eutectic reaction (L→α-Mg + W phase), which facilitates healing of the incurred cracking. Conversely, the Mg-5Zn-2.5Er alloy shows inferior feeding ability due to the lowest solid phase fraction (98.3%), wide freezing range (199.5 °C), and lowest permeability. Therefore, the Mg-5Zn-2.5Er alloy exhibits maximal hot cracking susceptibility, and the Mg-5Zn-5Er alloy exhibits minimal hot cracking susceptibility. This work provides guidance for improving the hot cracking resistance of cast Mg-Zn-Er alloy and enables an understanding of the hot cracking behaviors of Mg-Zn-RE alloys.

Positive associations between menstrual lifespan, geriatric depression and healthy longevity in Chinese oldest-old and centenarian women.

OBJECTIVE: Menstrual lifespan (ML) is an important biological characteristic for women. Rare evidence has established the associations between menopause age (MI), geriatric depression and healthy longevity. This study aimed to address these associations in Chinese oldest-old and centenarian women, and explore their related factors in order to provide strategy support for healthy aging. METHODS: The China Hainan Centenarian Cohort Study provides a population-based sample in Hainan, China. A total of 723 women including 318 centenarian women and 405 oldest-old women aged 80-99 years were included in this study. Data on demographic information were collected using a structured questionnaire. Physical examination and blood samples were obtained following standard procedure. Geriatric Depression Scale (GDS-15) was used to evaluate depressive symptoms for all participants. RESULTS: The proportions of participants with depression and longevity were 19.78 % (143 older adults) and 43.98 % (318 older adults), respectively. After adjusting for a wide range of other covariates in multiple logistic regression analyses, ML was positively and significantly associated with depression and longevity [Exp(ß) 1.076 and 1.121; P < 0.05 for all]. In multiple linear regression analyses, there were significantly positive associations of ML with GDS-15 (ß = 0.061) and age (ß = 0.238, p < 0.05 for all) after adjusting for all covariates. CONCLUSIONS: This study provides epidemiological evidence that menstrual lifespan has positive associations with geriatric depression and healthy longevity in Chinese oldest-old and centenarian women. Future researches should focus on the effects of intervening MI on psychological health and successful longevity.

The stool syndecan2 methylation test is more robust than blood tests for methylated septin9, CEA, CA19-9 and CA724: a diagnostic test for the early detection of colorectal neoplasms.

Background: Methylated syndecan2 (mSDC2) in stool samples has been found to be associated with colorectal cancer (CRC) and precancerous lesions. However, the available data are limited, and no previous studies have compared the analysis of mSDC2 with other diagnostic tests. Thus, we aimed to evaluate the clinical performance of a stool mSDC2 test and compare its performance with that of blood-based tests for methylated septin9 (mSEPT9), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA724) in detecting colorectal neoplasms. Methods: The gold standard diagnostic technique that was used was colonoscopy combined with a pathological analysis of biopsied tissue. Stool DNA was extracted from 1,002 stool samples (445 from CRCs, 115 from adenomas, and 442 from controls) and then bisulfite-converted, followed by real-time quantitative methylation-specific polymerase chain reaction. Blood mSEPT9 levels were quantified by the Epi proColon 2.0 assay, and serum CEA, CA19-9 and CA724 levels were measured by electrochemiluminescence. The main indexes used during the evaluation were sensitivity, specificity and the area under the receiver operating characteristic curve (AUC). Results: Stool mSDC2 detected 69.7% of CRCs, which was significantly higher than 53.8% by plasma mSEPT9, 37.2% by CEA, 13.1% by CA19-9 and 17.5% by CA724; for adenoma, the detection rates were 31.3%, 11.1%, 2.3% and 11.9%, respectively. The AUC of mSDC2 in detecting CRC was 0.83, compared to 0.72, 0.75, 0.63 and 0.54 for mSEPT9, CEA, CA19-9 and CA724, respectively. mSDC2 identified patients with stage I-III CRC with a sensitivity of 71.6%, which was significantly higher than that of mSEPT9, CEA, CA19-9 and CA724 (54.2%, 35.5%, 11.9%, and 15.0%, respectively); for stage IV CRC, the sensitivities of mSDC2, mSEPT9, CEA, CA19-9 and CA724 were 75.9%, 82.6%, 79.3%, 36.0% and 56.5%, respectively. SDC2 and CEA had a significantly higher sensitivity for distal CRC than for proximal CRC. Conclusions: The stool SDC2 methylation test had a better performance in detecting nonmetastatic CRC and adenoma than evaluations of mSEPT9, CEA, CA19-9 and CA724 in blood. Our findings could be used to modify approaches for CRC prevention and early detection.

Development of a compact linear accelerator to generate ultrahigh dose rate high-energy X-rays for FLASH radiotherapy applications.

PURPOSE: In recent years, the FLASH effect, in which ultrahigh dose rate (UHDR) radiotherapy (RT) can significantly reduce toxicity to normal tissue while maintaining antitumor efficacy, has been verified in many studies and even applied in human clinical cases. This work evaluates whether a room-temperature radio-frequency (RF) linear accelerator (linac) system can produce UHDR high-energy X-rays exceeding a dose rate of 40 Gy/s at a clinical source-surface distance (SSD), exploring the possibility of a compact and economical clinical FLASH RT machine suitable for most hospital treatmentrooms. METHODS: A 1.65 m long S-band backward-traveling-wave (BTW) electron linac was developed to generate high-current electron beams, supplied by a commercial klystron-based power source. A tungsten-copper electron-to-photon conversion target for UHDR X-rays was designed and optimized with Monte Carlo (MC) simulations using Geant4 and thermal finite element analysis (FEA) simulations using ANSYS. EBT3 and EBT-XD radiochromic films, which were calibrated with a clinical machine Varian VitalBeam, were used for absolute dose measurements. A PTW ionization chamber detector was used to measure the relative total dose and a plane-parallel ionization chamber detector was used to measure the relative normalized dose of each pulse. RESULTS: The BTW linac generated 300-mA-pulse-current 11 MeV electron beams with 29 kW mean beam power, and the conversion target could sustain this high beam power within a maximum irradiation duration of 0.75 s. The mean energy of the produced X-rays was 1.66 MeV in the MC simulation. The measured flat-filter-free (FFF) maximum mean dose rate of the room-temperature linac exceeded 80 Gy/s at an SSD of 50 cm and 45 Gy/s at an SSD of 67.9 cm, both at a 2.1 cm depth of the water phantom. The FFF radiation fields at 50 cm and 67.9 cm SSD at a 2.1 cm depth of the water phantom showed Gaussian-like distributions with 14.3 and 20 cm full-width at half-maximum (FWHM) values, respectively. CONCLUSION: This work demonstrated the feasibility of UHDR X-rays produced by a room-temperature RF linac, and explored the further optimization of system stability. It shows that a simple and compact UHDR X-ray solution can be facilitated for both FLASH-RT scientific research and clinical applications.

Stage III deficient mismatch repair colon patients get greater benefit from earlier starting oxaliplatin-based chemotherapy regimen.

We evaluate the prognostic value of chemotherapy and other prognostic factors on overall survival among colon patients with deficient mismatch repair (dMMR), and determine the optimum time to start chemotherapy after surgery. Data of 306 colon cancer patients with dMMR who received radical surgery were collected from three Chinese centers between August 2012 and January 2018. Overall survival (OS) was assessed with the Kaplan-Meier method and log-rank. Cox regression analysis were used to assess influencing prognosis factors. The median follow-up time for all patients was 45.0 months (range, 1.0-100). There was a nonsignificant OS benefit from chemotherapy for patients with stage I and stage II disease, including high-risk stage II disease (log-rank p: 0.386, 0.779, 0.921), and a significant OS benefit for patients with stage III and stage IV disease for receiving post-operation chemotherapy (log-rank p = 0.002, 0.019). Stage III patients benefitted from chemotherapy regimens that contained oxaliplatin (log-rank p = 0.004), and Starting chemotherapy with oxaliplatin treatment earlier resulted in better outcomes (95% CI 0.013-0.857; p = 0.035). Chemotherapy regimens containing oxaliplatin can prolong the survival time of stage III and IV dMMR colon cancer patients. This beneficial manifestation was more pronounced after starting chemotherapy treatment early post operation. High risk stage II dMMR colon patients including T4N0M0 cannot benefit from chemotherapy.

Delayed Recovery After Deep Brain Stimulation Surgery for Parkinson's Disease Under General Anesthesia-Cases Report.

Objective: Parkinson's disease (PD) is a neurodegenerative syndrome, and deep-brain stimulation (DBS) is an effective therapy for carefully screened patients with PD. However, delayed recovery after anesthesia, which occurs after taking prolonged general anesthesia for such patients, has been reported less frequently in literature. This report explores the possible causes of postoperative awakening delay in patients undergoing DBS surgery due to general anesthesia and provides a reference for anesthesia management of similar operations in the future. Case Presentation: Three patients with PD elective underwent DBS surgery. The first patients demonstrated walking disability, gait deficits, unstable posture, limb stiffness, and imbalance. The second demonstrated left limb static tremor, stiffness, and bradykinesia. The third demonstrated bradykinesia, rigidity, walking deficits, and decreased facial expression. These included two males and one female with a mean patient age of 60.7 ± 6.7year, weight of 63.7 ± 11 kg, the height of 163.3 ± 7.6 cm, and preoperative American Society of Anesthesiology rating of 2.3 ± 0.6. The preoperative Glasgow Coma Scale mean score was 15. All patients completed the operation under general anesthesia (the mean anesthesia time was 5.3 ± 1.1 h). The mean operation time was 252 ± 60 min. The mean bleeding volume was 50 ml, and the urine volume was 867 ± 569 ml. However, all the patients showed unconsciousness after 95 ± 22 min after stopping the anesthetic, and the respiratory function was in good condition, but they could not cooperate with anesthesiologists and had no response to the anesthesiologist's instructions. The mean hospital stay was 17 ± 7 days. All patients were discharged uneventfully. The average number of days patients followed up postoperatively was 171 ± 28.5 days. Motor and speech were improved significantly postoperatively in three patients compared with preoperatively. Taking anti-Parkinson medication was markedly reduced. There were no complications during postoperative follow-up. Conclusions: To prevent delayed recovery occurring after DBS surgery in Parkinson's disease, it is recommended to take scalp nerve block + general anesthesia to complete the procedure while avoiding general anesthesia.