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Yan Fu,1,* Hongji Pu,2,* Qun Huang,2,* Peng Qiu,2 Deyin Zhao,3 Yong Cheng1 1Department of Nursing, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Second Ward of General Surgery, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Cheng; Deyin Zhao, Email cy7107@163.com; 9168722@qq.comIntroduction: Critical limb ischemia (CLI) is a severe condition characterized by inadequate blood flow to the lower extremities, often leading to tissue damage and amputation. CLI is characterized by microcirculatory dysfunction, muscle tissue necrosis, and inflammation. Patients may suffer from the traumatic pain and the increase of plantar pressure, and foot care for patients with CLI has become the “last mile” to improve their life quality. Traditional shoe insoles often lack individual customization, failing to address the unique anatomical needs and hemodynamic characteristics of patients. The study aims to investigate the effects of this innovative intervention on improving the clinical outcomes, and quality of life in CLI patients.Methods and Analysis: This Critical Limb Ischemia Hemodynamic Insole Study is a randomized controlled study performed to explore the effect of a 3D printing insole on foot care of CLI patients. This study recruitment began on November 1, 2021. Patients with CLI confirmed by clinical symptoms and imaging were recruited as the research objects. Participants will be randomly assigned to either the experimental group, which will receive 3D-printed insoles customized based on their hemodynamics, or the control group, which will receive traditionally manufactured insoles. Both groups were followed up for up to 24 months after surgery, including claudication distance, claudication time, pain score, rehospitalization, etc.Trial Registration Number: ChiCTR2100051857.Keywords: 3D printing, insole, hemodynamics, critical limb ischemia

Tao Wang,1,2,&ast; Qianwen Yang,3,&ast; Yan Gao,2 Rongping Zhang,2 Chaoxin Zhou,2 Weifang Kong,1 Guojin Zhang,1 Xinyue Chen,4 Hong Pu,1 Lan Shang1 1Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4CT Collaboration, Siemens-Healthineers, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Pu; Lan Shang, Department of Radiology, The First Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, Sichuan Province, 60072, People’s Republic of China, Tel +86 13882267217, Fax +86 87294280, Email ph196797@163.com; shanglan8282@163.comPurpose: This study aimed to investigate clinical features and computed tomography (CT) manifestations of rifampicin primary drug-resistant pulmonary tuberculosis in Liangshan Yi Autonomous Prefecture.Patients and Methods: A total of 100 inpatients with confirmed primary rifampicin-resistant pulmonary tuberculosis were recruited from January 2020 to December 2022 at an infectious disease hospital located in the Liangshan Yi Autonomous Prefecture. Additionally, 100 inpatients with confirmed drug-susceptible pulmonary tuberculosis during the same period were matched to the rifampicin-resistant group based on gender, age, and ethnicity. The clinical characteristics of the two groups were recorded separately. Furthermore, the CT manifestations in these patients were independently analyzed by three radiologists.Results: The results showed that comorbid diabetes mellitus was more prevalent in the drug-resistant tuberculosis (DR-TB) group than in the drug-susceptible tuberculosis (DS-TB) group (9% vs 0%, p=0.0032). In terms of imaging presentation, DR-TB patients exhibited a higher frequency of calcifications (55% vs 35.00%, p=0.0068), greater median number of cavities (5 vs 2, p=0.0027), and larger maximum cavity diameter (52.08± 25.55 mm vs 42.72± 17.48 mm, p=0.0097). Additionally, bilateral involvement was more common in DR-TB patients at the site of the lesion (89% vs 76%, p=0.0246), with a higher prevalence in the right middle (82% vs 68%, p=0.0332), right lower (82% vs 68%, p=0.0332), left upper (91% vs 77%, p=0.0113), and left lower lobes (92% vs 66%, p< 0.0001). Conversely, the involvement of only one lobe was less frequent in patients with DR-TB than in those with DS-TB (4% vs 13%, p=0.0398), whereas the involvement of all five lobes was more common (68% vs 51%, p=0.0209).Conclusion: Patients with DR-TB exhibit a higher prevalence of severe imaging manifestations, highlighting the importance of CT in the early detection and diagnosis of DR-TB.Keywords: drug-resistant tuberculosis, drug-susceptible tuberculosis, tuberculosis, comorbid diabetes mellitus

Lizhu Liu,1,&ast; Xiaolin Pang,2,&ast; Ke Zhao,3,&ast; Yaxue Chen,4 Yanli Li,1 Ruimin You,1 Tingting Xu,5 Mengmei Liu,6 Lin Wu,7 Zhenhui Li,1 Hongjiang Pu8 1Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China; 2Department of Radiotherapy, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, People’s Republic of China; 3Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Nursing, Dazhou Vocational and Technical College, Dazhou, Sichuan, 635000, People’s Republic of China; 5Department of Oncology, The People’s Hospital of Chuxiong Yi Autonomous Prefecture, Chuxiong, 675000, People’s Republic of China; 6School of Public Health, Kunming Medical University, Kunming, 650000, People’s Republic of China; 7Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, People’s Republic of China; 8Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, 635000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenhui Li, Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China, Tel/Fax +86 87168179549, Email lizhenhui621@qq.com Hongjiang Pu, Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, 635000, People’s Republic of China, Tel/Fax +86 87168179549, Email puhongjiang@qq.comBackground: It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy.Purpose: The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II–III colorectal cancer (CRC).Methods: The retrospective cohort analysis was performed on patients with stage II–III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II–III CRC.Results: A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80– 2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52– 3.70; log-rank P=0.66).Conclusion: Patients over the age of 75 with stage II–III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II–III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.Keywords: colorectal cancer, adjuvant chemotherapy, recurrence-free survival, prognosis

Jing Huang,1,2,&ast; Hongjiang Pu,3,&ast; Jintao He,4 Xiaohu Tang5 1The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, People’s Republic of China; 3Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, People’s Republic of China; 4Kunming Medical University, Kunming, People’s Republic of China; 5Department of Rheumatology, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohu Tang, Department of Rheumatology, the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, 120 Guanghua Street, Wuhua District, Kunming, 650032, People’s Republic of China, Tel/Fax +86-871-63639262, Email h.tang0718@163.comBackground: Most cancer-related deaths around the globe are caused by lung cancer. The present treatments for metastatic non-small cell lung cancer (mNSCLC) are cytotoxic chemotherapy (CCT), targeted therapy (TT) and immunotherapy, but the benefit of the same regime varies greatly. Hence, it is important to identify biomarkers to predict the efficacy of modalities. Previous literature suggested certain parameters might be predictive factors. Nevertheless, the utility of these parameters is limited due to the types of solid tumors.Purpose: The study aimed to examine whether the lung immune prognostic index (LIPI) was related to outcomes of CCT, immune checkpoint inhibitors (ICIs) and TT for mNSCLC patients.Materials and Methods: A retrospective cohort study between September 2012 and May 2020 was conducted on 350 Chinese mNSCLC patients, including 147 patients receiving ICIs, 103 TT, and 100 CCT. The data were examined to analyze the prognostic value of LIPI among various treatments.Main Outcomes and Measures: The associations between PFS and good, intermediate, or poor prognostic LIPI scores in ICIs, TT, and CCT were determined, respectively.Results: In univariable analyses, there was a relevance between a good LIPI score and better PFS among patients receiving ICIs (HR, 0.81; 95% CI, 0.44– 1.51), TT (HR, 0.35; 95% CI, 0.16– 1.74), and CCT (HR, 0.39; 95% CI, 0.19– 0.80). In multivariable analyses, the intermediate LIPI score was linked to better PFS only in patients receiving TT (HR, 0.31; 95% CI, 0.17– 0.92) rather than ICIs (HR, 1.12; 95% CI, 0.66– 2.45) or CCT (HR, 1.24; 95% CI, 0.49– 4.55).Conclusion: Baseline LIPI value is an important prognostic biomarker for mNSCLC patients treated with TT. Shorter PFS with TT was associated with poor baseline LIPI. Poor LIPI score may be considered as a promising indicator showing which patients are unlikely to respond well to TT. The prognostic value of LIPI can be more clearly determined through prospective clinical study.Keywords: lung immune prognostic index, metastatic non-small cell lung cancer, prognostic value

Hongjie Qian,1,2 Qian Chen,1,2 Liyu Liang,1,2 Yang Zou,1,2 Huahua Pu,1,2 Liang Xin,1,2 Rong Song,1,2 Tingting Li,1,2 Huijuan Zhu,1,2 Yu Wang,3 Guanghui Tian,4 Jingshan Shen,2,3 Hualiang Jiang,2,3 Chen Yu,1,2 Zhen Wang,2,3 Jingying Jia1,2 1Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, 200031, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, 200031, People’s Republic of China; 3CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China; 4Vigonvita Life Science Co., Ltd., Suzhou, 215123, People’s Republic of ChinaCorrespondence: Jingying JiaShanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, 200031, People’s Republic of ChinaTel/Fax +86 21 54030254Email jyjia@shxh-centerlab.comZhen WangShanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zu Chong Zhi Road, Pudong, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20231000Fax +86 21 20231962Email wangzhen@simm.ac.cnPurpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H.Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: In Part I, AUC and Cmax were proved to be linear within the 5– 30 mg dose range. T1/2 of TPN171H was 8.02– 10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease Cmax, prolong Tmax, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and Cmax indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination.Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.Keywords: TPN171H, PDE5 inhibitor, safety, pharmacokinetics, food effect, healthy subjects

Jingtai Chen,1,&ast; Zhou Xu,1,&ast; Lingmi Hou,1 Yunhui Tang,1 Shuangqiang Qian,1 Hongyu Pu,1 Juan Tang,2 Yanchun Gao1 1Department of Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People’s Republic of China; 2Department of Burns and Plastic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanchun GaoDepartment of Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of ChinaEmail boyang11111@163.comObjective: Based on physical examination, to explore the relationship between breast mass (BM) and thyroid nodule (TN) prevalence, and to further explore other related factors that affect the occurrence of BM and TN.Methods: From January 1, 2018, to January 1, 2021, 12,538 female subjects received breast and thyroid ultrasound examinations at the same time in the health examination center of the Affiliated Hospital of North Sichuan Medical College. Univariate analysis and multivariate logistic analysis were used to screen the relevant factors affecting TN and BM, and propensity score matching was used to further verify the results of the relationship between breast and thyroid.Results: A total of 4975 (39.7%) of the included subjects have BM and a total of 6315 (50.4%) have TN,2557 (20.4%) had both BM and TN. The logistic regression results show that patients with TN are more likely to suffer from BM [OR = 1.185, 95% CI (1.099– 1.278), p< 0.0001]. In addition, age, free T4, HDL, height, BMI, systolic blood pressure, diastolic blood pressure, and albumin are independent factors affecting the occurrence of BM; patients with BM are more likely to have TN [OR = 1.180, 95% CI (1.094– 1.272), p< 0.0001], and age, free T3, free T4, AST, ALT, albumin, height, and BMI are independent influencing factors on the occurrence of TN. The result of propensity score matching confirmed the relationship between BM and TN.Conclusion: There is a bidirectional pathogenic relationship between BM and TN, women with BM are at increased risk of TN, and women with TN are more likely to have BM. Thyroid hormone is not only related to the occurrence of TN but also affects the occurrence of BM.Keywords: breast, thyroid, nodule, propensity score analysis

Hongjiang Pu,1,* Peiyi Xie,2,* Yaxue Chen,3,* Yanrong Zhao,4 Xi Ye,5 Guiyu Lu,4 Dafu Zhang,6 Zhenhui Li6 1Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, 635000, People’s Republic of China; 2Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, People’s Republic of China; 3Department of Nursing, Dazhou Vocational and Technical College, Dazhou, Sichuan, 635000, People’s Republic of China; 4Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China; 5Department of Oncology, The First People’s Hospital of Honghe State, Mengzi, 661100, People’s Republic of China; 6Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, 650118, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dafu Zhang; Zhenhui LiDepartment of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Centre, Kunming, Yunnan, 650118, People’s Republic of ChinaTel/ Fax +86 87168179594; +86 87168179549Email tosney@126.com; lizhenhui621@qq.comPurpose: Based on a multi-centered and a large sample size, this study aims to analyze the relationship between preoperative and postoperative serum CEA and recurrence of rectal cancer without preoperative therapy.Methods: This retrospective cohort study enrolled stage I to III rectal cancer patients without preoperative therapy (N = 1,022) who received radical resection of rectal cancer from 2 hospitals in China. Based on the preoperative and postoperative serum carcinoembryonic antigen, the patients were subdivided into 3 groups ie, normal preoperative CEA (≤ 5.0 ng/mL, N = 627), elevated preoperative (> 5.0 ng/mL) but normalized postoperative CEA (normalized postoperative CEA, N = 255), as well as elevated preoperative and postoperative CEA (elevated postoperative CEA, N = 67). The generalized additive model was used to assess the relationship between carcinoembryonic antigen and the risk of recurrence. Further, the Cox regression model was used to evaluate the relationship between carcinoembryonic antigen and 3-year recurrence-free survival (RFS) after adjusting for potential confounders.Results: The 3-year RFS of patients with elevated postoperative CEA was 45.8% (95% CI, 35.2% − 59.5%), which was significantly lower compared to the other two groups of patients (normalized postoperative CEA: 75.9%, 95% CI, 70.8%-81.4%; and normal preoperative CEA: 84.9%, 95% CI, 82.2%-87.8%) (P < 0.001). Based on multivariable Cox model analysis, the elevated postoperative CEA was a prognostic factor for 3 years RFS (hazard ratio [HR], 3.08; 95% CI, 2.05– 4.66; P< 0.001). At the same time, normalized postoperative CEA was insignificantly correlated with 3-year RFS (HR, 1.38; 95% CI, 1.00– 1.92; P = 0.05) and was not an independent risk factor.Conclusion: We found that preoperative and postoperative serum CEA of rectal cancer patients were related to the 3-year recurrence-free survival rate. Moreover, the risk of recurrence in the normalized postoperative CEA group of patients was insignificantly different from that of the normalized preoperative CEA patients. Therefore, it is necessary to combine preoperative and postoperative CEA to predict the prognosis of patients with rectal cancer, rather than using it alone.Keywords: preoperative and postoperative serum CEA, rectal cancer, RFS

Zhenhui Li,1,* Shaoyou Li,2,* Yun Liang,3,* Hongjiang Pu,4 Changling Tu,5 Zhenyu Wu,6 Dingyun You7,8 1Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 4Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 5Department of Cadres Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, People’s Republic of China; 7The Department of Epidemiology & Biostatistics, School of Public Health, Kunming Medical University, Kunming, Yunnan 650500, People’s Republic of China; 8Yunnan Key Laboratory of Laboratory Medicine, Kunming Medical University, Kunming, Yunnan 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dingyun YouYunnan Key Laboratory of Laboratory Medicine, Kunming Medical University, No. 1168 Chunrongxi Road, Chenggong District, Kunming, Yunnan 650500, People’s Republic of ChinaTel/ Fax +86 871-5922935Email youdingyun@qq.comZhenyu WuDepartment of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, 130 Dongan Road, Shanghai, People’s Republic of ChinaTel/ Fax +86 21‐33563913Email nc.ude.naduf@wyzObjective: Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer (CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients.Patients and Methods: Consecutive stage I–III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed.Results: A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3% [95% CI 65.7– 75.2%] vs 77.6% [95% CI 73.7– 81.7%] and unadjusted hazard ratio [HR] 1.36 [95% CI 1.04– 1.78], P= 0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12– 0.72], P=0.008).Conclusion: Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy.Keywords: recurrence, peripheral CD4+ T cells, colorectal cancer, adjuvant chemotherapy, propensity score matching analysis

The GLT project is deploying a new submillimeter (submm) VLBI station in Greenland. Our primary scientific goal is to image a shadow of the supermassive black hole (SMBH) of six billion solar masses in M87 at the center of the Virgo cluster of galaxies. The expected SMBH shadow size of 40-50 μas requires superbly high angular resolution, suggesting that the submm VLBI would be the only way to obtain the shadow image. The Summit station in Greenland enables us to establish baselines longer than 9,000 km with ALMA in Chile and SMA in Hawaii as well as providing a unique u–v coverage for imaging M87. Our VLBI network will achieve a superior angular resolution of about 20 μas at 350 GHz, corresponding to ∼ 2.5 times of the Schwarzschild radius of the supermassive black hole in M87. We have been monitoring the atmospheric opacity at 230 GHz since August. 2011; we have confirmed the value on site during the winter season is comparable to the ALMA site thanks to high altitude of 3,200 m and low temperature of −50°C. We will report current status and future plan of the GLT project towards our expected first light on 2015–2016.

Abstract Solid Earth tide represents the response of solid Earth to the lunar (solar) gravitational force. The yielding solid Earth due to the force has been thought to be a prolate ellipsoid since the time of Lord Kelvin, yet the ellipsoid’s geometry such as major semi-axis’s length, minor semi-axis’s length, and flattening remains unresolved. Additionally, the tidal displacement of reference point is conventionally resolved through a combination of expanded potential equations and given Earth model. Here we present a geometric model in which both the ellipsoid’s geometry and the tidal displacement of reference point can be resolved through a rotating ellipse with respect to the Moon (Sun). We test the geometric model using 23-year gravity data from 22 superconducting gravimeter (SG) stations and compare it with the current model recommended by the IERS (International Earth Rotation System) conventions (2010), the average Root Mean Square (RMS) deviation of the gravity change yielded by the geometric model against observation is 6.47 µGal (equivalent to 2.07 cm), while that yielded by the current model is 30.77 µGal (equivalent to 9.85 cm). The geometric model will greatly contribute to many application fields such as geodesy, geophysics, astronomy, and oceanography.

Purposes To achieve the reuse of solid waste, the feasibility of using compacted tailings-bentonite material as an impermeable material for landfill cover system is explored in this study. The maximum dry density values of tailings-bentonite mixtures with varying bentonite contents are determined through compaction tests. Methods Saturated permeability coefficients of the tailings-bentonite mixtures were measured by using a consolidation permeameter. Additionally, the pore characteristics of the samples were analyzed through mercury intrusion porosimetry and scanning electron microscopy tests. Finally, the service performance of compacted tailings-bentonite mixture in cover systems was investigated by using numerical simulations. Findings The results reveal that the maximum dry density of the tailings-bentonite mixture first increases and then decreases with increasing bentonite content, reaching the maximum of 1.94 g/cm3 at 10% bentonite content. The permeability coefficient of the compacted tailings-bentonite mixture decreases with the increase of bentonite content. A bentonite content of 10% or higher satisfies the permeability requirement for the impermeable layer, i.e., ks=5.61×10-10 m/s, ≤10-9 m/s; in this case, an impermeable layer with a thickness of 10 cm meets the requirement that annual percolation ≤30 mm. Additionally, setting a certain slope to facilitate lateral drainage can effectively reduce the percolation through landfill cover system.

Effective subunit vaccines for tuberculosis (TB) must target antigenic components at various stages of infection. In this study, we constructed fusion proteins using secreted antigens from Mycobacterium tuberculosis (M. tuberculosis), specifically ESAT6, CFP10, MPT64, and Rv2645 from the proliferation stage, along with latency-associated antigens Rv1738 and Rv1978. The resulting fusion proteins, designated LT33 (ESAT6-CFP10-Rv1738) and LT28 (MPT6461-170-Rv19788-60-Rv264521-80), were combined with an adjuvant containing dimethyldioctadecylammonium bromide (DDA), polyriboinosinic polyribocytidylic acid (PolyI:C), and cholesterol to construct subunit vaccines. We evaluated the subunit vaccine effect in C57BL/6 mice and revealed that LT33 and LT28 exhibited strong immunogenicity and induced protective efficacy against aerosol challenge with M. tuberculosis H37Rv. Notably, the combination of LT33 and LT28 led to a significant reduction of 0.77 log10 colony-forming units (CFU) of H37Rv in the lungs compared to the adjuvant control group, highlighting their potential as promising candidates for subunit vaccine against M. tuberculosis infection.

The ovules or seeds (fertilized ovules) with wings are widespread and especially important for wind dispersal. However, the earliest ovules in the Famennian of the Late Devonian are rarely known about the dispersal syndrome and usually surrounded by a cupule. From Xinhang, Anhui, China, we now report a new taxon of Famennian ovules, Alasemenia tria gen. et sp. nov. Each ovule of this taxon possesses three integumentary wings evidently extending outwards, folding inwards along abaxial side and enclosing most part of nucellus. The ovule is borne terminally on smooth dichotomous branches and lacks a cupule. Alasemenia suggests that the integuments of the earliest ovules without a cupule evolved functions in probable photosynthetic nutrition and wind dispersal. It indicates that the seed wing originated earlier than other wind dispersal mechanisms such as seed plume and pappus, and that three- or four-winged seeds were followed by seeds with less wings. Mathematical analysis shows that three-winged seeds are more adapted to wind dispersal than seeds with one, two or four wings under the same condition.

Background In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses.Methods To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme−/− ID8 tumor cells into C57BL/6 mice.Results Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1–caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model.Conclusions PARPis induce a specific type of ICD called pyroptosis via TNF–caspase 8–GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions.Trial registration number NCT04507841.

CO2 sequestration via mineralization of steel slag has received widespread attention due to its ability to achieve in-situ CO2 sequestration in steel industries and high-value utilization of steel slag. The final CO2 sequestration capacity of steel slag is closely related to the reaction parameters (i.e., reaction duration, reaction temperature, CO2vol concentration, and liquid-solid ratios) of mineralization. The reaction parameters may have synergistic effects on the ability of steel slag to sequestrate CO2. Therefore, the single-factor (one-factor-at-a-time) experimental strategy can't obtain optimal process parameters. Herein, response surface methodology and the Box-Behnken Design were employed in determining optimal conditions. It is found that the combined effects of CO2 concentration in combination with reaction temperature and liquid-solid ratio significantly influence the sequestration process (P = 0.0082 and P < 0.0001, respectively). Conversely, the combined effects of reaction duration with liquid-solid ratio and CO2 concentration were found to be less significant (P = 0.6905 and P = 0.6114, respectively). The reasons behind this observation can be ascribed to the focus of this research on the later stages of the reaction, during which it proceeds smoothly. Additionally, alterations in temperature, liquid-solid ratio, and CO2 concentration not only affect the initial pH, CO2 dissolution rate and quantity, and reaction kinetics but also alter the patterns of their collective impact on CO2 sequestration. The CO2 capture could reach 179.1 g-CO2/kg-steel slag at the optimal condition (i.e., 56.14 °C reaction temperature, 6.66 ml/g liquid-solid ratio, 44.53 wt.% CO2 concentration, and 286.73 mins reaction time), compared to single-factor stepwise optimization, which improves by about 9.84 %. Implementing this optimized mineralization process could enable the Chinese steel industry to capture an estimated 27.4 million tons of CO2 annually, based on an annual production of 153 million tons of steel slag.

Abstract The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.

Abstract Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Abstract Background While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. Methods FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. Results Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. Conclusions Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

Abstract The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.

The temperature control of the air-cooled proton exchange membrane fuel cell (PEMFC) is important for effective and safe operation. To develop a practical and precise controller, this study combines the Radial Basis Function (RBF) neural network with Back Propagation neural network adaptive Proportion Integration Differentiation (BP-PID), and then a metaheuristic algorithm is used to optimize the parameters of RBF-BP-PID for further improvement in temperature control. First, an air-cooled PEMFC system model is established. To match the simulation data with the experimental data, Teaching Learning Based Optimization–Differential Evolution (TLBO-DE) is proposed to identify the unknown parameters, and the maximum relative error is

BackgroundModern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques.MethodsWe enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients.ResultsUsing predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability.ConclusionIn summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.

ABSTRACT The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages.IMPORTANCEThe highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.

This study proposes a new method using the combination of flocculation and prefabricated horizontal drain (PHD) assisted with vacuum pressure for rapid dewatering of high-water-content dredged slurry. First, to demonstrate the superiority of using PHD over the more commonly used prefabricated vertical drain (PVD), experiments were conducted to compare the dewatering performance between the PHD and the PVD. Then six model tests with the proposed dewatering method were performed with various contents of flocculant (anionic polyacrylamide (APAM)) to investigate the effect of APAM content on the dewatering process and soil properties (i.e. undrained shear strength, permeability and compressibility). Furthermore, particle size distributions of the slurry before and after model tests were measured to analyze the dewatering behavior and changes in material properties. Finally, particle loss during vacuum consolidation for various APAM contents were compared to study the flocculation effect on clogging problem. Results indicate that the proposed method can prevent significant bending deformation of the drain board and mitigate clogging of the drain filter and, thus, can significantly accelerate the dewatering process of high-water-content dredged slurry. [ABSTRACT FROM AUTHOR]

Recently, the high proportion of methicillin-resistant Staphylococcus aureus infections worldwide has highlighted the urgent need for novel antibiotics to combat this crisis. The recent progress in computational techniques for use in health and medicine, especially artificial intelligence (AI), has created new and potential approaches to combat antibiotic-resistant bacteria, such as repurposing existing drugs, optimizing current agents, and designing novel compounds. Halicin was previously used as a diabetic medication, acting as a c-Jun N-terminal protein kinase (JNK) inhibitor, and has recently demonstrated unexpected antibacterial activity. Although previous efforts have highlighted halicin’s potential as a promising antibiotic, evidence regarding its effectiveness against clinical strains remains limited, with insufficient proof of its clinical applicability. In this study, we sought to investigate the antibacterial activity of halicin against MRSA clinical strains to validate its clinical applicability, and a C. elegans model infected by MRSA was employed to evaluate the in vivo effect of halicin against MRSA. Our findings revealed the antibacterial activity of halicin against methicillin-resistant S. aureus clinical strains with MICs ranging from 2 to 4 µg/mL. Our study is also the first work to evaluate the in vivo effect of halicin against S. aureus using a C. elegans model, supporting its further development as an antibiotic.

Background Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral‐cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke‐induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. Methods and Results In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3‐deficient mice in combination with Smart‐seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke‐induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte‐derived macrophages into the heart. Subsequently, we identified that cardiac monocyte‐derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3‐deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte‐derived macrophages and subsequent cardiac dysfunction. Conclusions Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve–monocyte‐derived macrophage axis.

Colitis caused by infections, especially Salmonella, has long been a common disease, underscoring the urgency to understand its intricate pathogenicity in colonic tissues for the development of effective anti-bacterial approaches. Of note, colonic epithelial cells, which form the first line of defense against bacteria, have received less attention, and the cross-talk between epithelial cells and bacteria requires further exploration. In this study, we revealed that the critical anti-bacterial effector, TFEB, was primarily located in colonic epithelial cells rather than macrophages. Salmonella-derived LPS significantly promoted the expression and nuclear translocation of TFEB in colonic epithelial cells by inactivating the mTOR signaling pathway in vitro, and this enhanced nuclear translocation of TFEB was also confirmed in a Salmonella-infected mouse model. Further investigation uncovered that the infection-activated TFEB contributed to the augmentation of anti-bacterial peptide expression without affecting the intact structure of the colonic epithelium or inflammatory cytokine expression. Our findings identify the preferential distribution of TFEB in colonic epithelial cells, where TFEB can be activated by infection to enhance anti-bacterial peptide expression, holding promising implications for the advancement of anti-bacterial therapeutics.

Abstract The possibilities of cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and important livestock species are not yet known. Herein, we used the structural and genetic alignment and surface potential analysis of the amino acid (aa) in angiotensin-converting enzyme 2 (ACE2), tyrosine kinase receptor UFO (AXL), and neuropilin 1 (NRP1) in different species with substantial public health importance. The residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of S were aligned to screen the critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host. We found that AXL and NRP1 proteins might be used as the receptors of SARS-CoV-2 in bovines. However, ACE2 protein may not be considered to be involved in the cross-species transmission of SARS-CoV-2 VOCs in cattle because the key residues of the ACE2-S-binding interface were different from those in known susceptible species. This study indicated that emerging SARS-CoV-2 variants potentially expand species tropism to bovines through AXL and NRP1 proteins.

Background The competency in primary performance positions of rural order-oriented medical graduates of standardized general residency training program (abbreviate for oriented general practitioners) has attracted wide attention. Strengthening continuing medical education is an important measure to enhance the competency of oriented general practitioners. Objective To understand the current situation, problems and needs of continuing medical education for oriented general practitioners in Guizhou Province, and to provide a basis for improving continuing medical education for oriented general practitioners. Methods From November to December 2021, 42 oriented general practitioners from 39 township hospitals in 9 cities in Guizhou Province were selected as the research subjects for semi-structured interviews by the purposive sampling and snowball sampling methods. The interview results were coded and analyzed by the research method of procedural grounded theory to extract and summarize the current situation, problems and needs of their continuing medical education. Results After three-level coding, 145 concepts, 23 categories and 5 domains related to the continuing medical education of oriented general practitioners were finally sorted out, and a story line was consequenty formed: the continuing medical education of oriented general practitioners is influenced by several factors, among which actual situation is the obstacle, competency requirement is the extrinsic driver, policy system is important guarantee, self-demand is the intrinsic motivation, and the improvement of the training process management is the key process. Conclusion The training intention of oriented general practitioners remains to be strengthened in Guizhou Province. The quality of continuing medical education, integration degree of training content and demand, and attention of primary care institutions need to be improved. The support for continuing medical education and the construction of information platform should be strengthened, and the content and form of continuing medical education suitable for oriented general practitioners should be improved, in order to improve the quality and effect of training in continuing medical education.

Abstract During the last two decades, two-dimensional (2D) materials have been the focus of condensed matter physics and material science due to their promising fundamental properties and (opto-)electronic applications. However, high-κ 2D dielectrics that can be integrated within 2D devices are often missing. Here, we propose nonlayered oxide monolayers with calculated exfoliation energy as low as 0.39 J/m2 stemming from the ionic feature of the metal oxide bonds. We predict 51 easily or potentially exfoliable oxide monolayers, including metals and insulators/semiconductors, with intriguing physical properties such as ultra-high κ values, negative Poisson’s ratios and large valley spin splitting. Among them, the most promising dielectric, GeO2, exhibits an auxetic effect, a κ value of 99, and forms type-I heterostructures with MoSe2 and HfSe2, with a band offset of ~1 eV. Our study opens the way for designing nonlayered 2D oxides, offering a platform for studying the rich physics in ultra-thin oxides and their potential applications in future information technologies.

The aim of this study was to analyze the role of Ezrin in esophageal squamous cell carcinoma (ESCC) and investigate potential therapeutic targets for ESCC by interfering with Ezrin expression. Bioinformatics analysis revealed that Ezrin expression differed significantly among patients with different clinical stage ESCC. Moreover, there was a significant correlation between Ezrin and yes-associated protein/connective tissue growth factor (YAP1/CTGF) levels in esophageal cancer. Sixty paraffin-embedded ESCC tissue samples were examined and Ezrin and YAP1/CTGF levels were determined using immunohistochemistry. The positive expression rates of Ezrin and YAP1/CTGF were significantly lower in adjacent tissues than in ESCC tissues. Furthermore, knockdown of Ezrin expression inhibited colony formation and reduced cell migration and invasion. Compared with control ESCC cells, protein expression levels of YAP1 and CTGF were significantly downregulated in cells with Ezrin knocked down. We conclude that Ezrin may be involved in ESCC progression through the Hippo signaling pathway.

Abstract The myocardial single photon emission computed tomography (SPECT) is a good study due to its clinical significance in the diagnosis of myocardial disease and the requirement for improving image quality. However, SPECT imaging faces challenges related to low spatial resolution and significant statistical noise, which concerns patient radiation safety. In this paper, a novel reconstruction system combining multi-detector elliptical SPECT (ME-SPECT) and computer tomography (CT) is proposed to enhance spatial resolution and sensitivity. The hybrid imaging system utilizes a slit-slat collimator and elliptical orbit to improve sensitivity and signal-to-noise ratio (SNR), obtains accurate attenuation mapping matrices, and requires prior information from integrated CT. Collimator parameters are corrected based on CT reconstruction results. The SPECT imaging system employs an iterative reconstruction algorithm that utilizes prior knowledge. An iterative reconstruction algorithm based on prior knowledge is applied to the SPECT imaging system, and a method for prioritizing the reconstruction of regions of interest (ROI) is introduced to deal with severely truncated data from ME-SPECT. Simulation results show that the proposed method can significantly improve the system's spatial resolution, SNR, and image fidelity. The proposed method can effectively suppress distortion and artifacts with the higher spatial resolution ordered subsets expectation maximization (OSEM); slit-slat collimation.

SF6 is widely developed and applied in gas insulated electrical equipment due to its excellent arc extinguishing performance and insulation performance. However, SF6 is very destructive to the ozone layer and has a strong cumulative effect on the greenhouse effect of global warming. Therefore, the inevitable trend of the development of power grid equipment in the future is to reduce or even prohibit the use of SF6 gas in the power system, power industry and electrical equipment, or to find insulation media that can replace SF6. As a result, the research on environment-friendly insulating gas has become popular. In this paper, power frequency partial discharge platform and GC–MS​ detection platform are used to systematically study the partial discharge and decomposition characteristics of C5F10O under N2 and CO2 background gases. The partial discharge extinction voltage (PDIV) and partial discharge statistical characteristics of C5F10O under two different background gases, as well as the variety and concentration change of mixed gas decomposition products are theoretically analyzed and compared with SF6. It is found that, similar to SF6, the PDIV of C5F10O under two kinds of background gases increases linearly with the increase of air pressure. The PDIV under N2 background is smaller than that under CO2 background under the same conditions, and its insulation performance is slightly better than that under CO2 background. The partial discharge decomposition of C5F10O mixed gas mainly produces fluorocarbons such as CF4, C2F4, C2F6, C3F8, C3F6, and a small amount of CO, COF2, C3HF7, and CHF3. The increase of air pressure inhibits the partial discharge decomposition of mixed gas.

Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. In the process of immune regulation, USP5 affects important cellular signaling pathways, such as NF-κB, Wnt/β-catenin, and IFN, by regulating ubiquitin-dependent protein degradation. These pathways play important roles in immune regulation and inflammatory responses. In addition, USP5 regulates the activity and function of immunomodulatory signaling pathways via the deubiquitination of key proteins, thereby affecting the activity of immune cells and the regulation of immune responses. In the present review, the structure and function of USP5, its role in immune regulation, and the mechanism by which USP5 affects the development of diseases by regulating immune signaling pathways are comprehensively overviewed. In addition, we also introduce the latest research progress of targeting USP5 in the treatment of related diseases, calling for an interdisciplinary approach to explore the therapeutic potential of targeting USP5 in immune regulation.

key to satisfy people’s demand for consumption of livestock and poultry products. This study focused on the strategic requirements of ensuring food security and achieving sustainable protein supply, and analyzed the utilization status of protein feed resources and summarized the major problems in protein feed supply. Based on the protein feed resources in China and the potential of protein supply in the international market, this article analyzed the potential for substituting soybean meal in our country. It is expected that by 2035 the soybean imports will have reduced 58.8 million tons compared with 2020 by expanding the planting, increasing the income of oil crops, developing new feed resources, utilizing conventional protein feed resources, efficiently, optimizing the planting structure of forage crops, as well as improving the efficiency of livestock and poultry protein conversion. It is suggested that future efforts should be focused on tapping potentials and expanding resources, strengthening scientific and technological support, also carrying out appropriate import by imptementing major projects such as increasing crop and forage production, improving quality and efficiency of unconventional protein feed resources, and developing new protein feed resources. In addition, financial support should be increased and the international market effectively exploited, in order to promote soybean meal substitution and ensure national food security.