[Analysis of non-alcoholic fatty liver disease differences from metabolic dysfunction-associated fatty liver disease based on clinical features].

Objective: To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames. Methods: Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ(2) test. Results: NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m(2), respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) µmol/L, (346.57 ± 89.49) µmol/L, and (344.89 ±89.67) µmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) µmol/L, 73.0 (65.0, 83.5) µmol/L, and 73.0 (65.0, 83.0) µmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences (P<0.05). Conclusion: Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

[Analysis on the trend of liver cancer morbidity and mortality in certain district, Suzhou City, Jiangsu Province, 2017 to 2019].

Objective: To analyze the trend of liver cancer morbidity and mortality among residents with household registration in certain District, 2017 to 2019. Methods: The crude morbidity and mortality rate of males and females in the whole population were calculated by using the relevant data from the certain District Cancer Registry and Report System and the Cause of Death Surveillance System. The standardized morbidity and mortality rate were calculated according to the age structure of 2000 National Demographic Census and Segi's world population, respectively. Trend in liver cancer morbidity and mortality were evaluated using percent change (PC), annual percentage change, and case-number-weighted annual percent change. Age-specific rates were used to analyze the epidemic trend of liver cancer with age. Results: The crude morbidity rate of liver cancer in the whole population (male and female) of the certain district from 2017 to 2019 were 18.86/100 000, 26.05/100 000 and 11.90/100 000 respectively, and the crude mortality rates were 21.20/100 000, 29.29/100 000 and 13.38/100 000 respectively. The crude morbidity and mortality rate of liver cancer among male showed a downward trend (PC=-16.77% and -20.15% respectively). The crude morbidity and mortality rate of liver cancer among female showed inconsistent changes; however, the crude morbidity rate showed a downward trend, and the crude mortality rate first increased and then decreased (PC=-19.42% and -0.30% respectively). Liver cancer morbidity and mortality rate in male after the age of 30 were increased with age. The two key points of accelerated growth were around the age of 65 and 75, and the peak of morbidity (130.78/100 000) and mortality (201.96/100 000) were after the age of 80. The morbidity and mortality rate were significantly lower in female than those of male aged 60; however, after the age of 65, the morbidity rate was increased rapidly and gradually approached as that of male. After the age of 80 (the peak morbidity and mortality were 104.40/100,000 and 132.87/100,000, respectively), male were about twice as high as those female aged between 75 and 79. Conclusion: Morbidity and mortality rate of liver cancer in the certain District showed an overall downward trend from 2017 to 2019, but it increased with age, and the disease burden was relatively high among the elderly population. Liver cancer mostly occurred in male, so the prevention and control of liver cancer epidemics in middle-aged and elderly should be actively monitored.

[Safety and efficacy of left atrial appendage closure combined with patent foramen ovale closure for atrial fibrillation patients with patent foramen ovale].

Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.

[Study on human fatigue during monotonous sitting-posture work].

Objective: In this study, the occupational fatigue caused by long-time sitting-posture work was studied. Also, the physical and psychological factors which affect on human fatigue of workers suffering from monotonous sitting-position were analyzed. Methods: In 2021, a total of 30 subjects, including 15 males and 15 females, were selected to complete a 4-hour simulated sitting-position assembly task in the laboratory. The "Borg's RPE" was used to measure the subjects' subjective fatigue and feeling of monotony, the polyconductive physiological recorder was used to measure the subjects' EMG, and the wireless motion-capture evaluation system was used to measure the kinematics of the subjects. Results: When engaged in monotonous work tasks, there was a significant positive correlation between workers' monotony and subjective fatigue, with correlation coefficients ranging from 0.976 to 0.988 (P<0.050) . At the beginning of work, the subjective fatigue of the neck was more significant (P=0.046) . As working time increased, the back fatigue was significantly higher than that of the neck (P=0.029) . After 4 hours of work, the MPF value of the back erector spinae EMG decreased significantly (P=0.025) . The body posture data showed that the shoulder and neck indicators began to change significantly after about 2 hours of work (P(neck)=0.032, P(shoulder)=0.021) . The waist and hip indicators began to change significantly after about 4 hours of work (P(left hip)=0.031, P(right hip)=0.028) . The flexion angle of the neck first increased and then decreased; the flexion angle of the waist and hip continued to increase with the working time. Conclusion: It was found that the fatigue effect of monotonous sitting-posture work on the operator is mainly reflected in the lower back. The monotony of the work exacerbates the operator's subjective fatigue feeling. The operator should be given corresponding protection and set the work content reasonably. It is recommended to have appropriate activities or short breaks every 2 work-hour.

Deliberating Performance Targets: Follow-on workshop discussing PM10, NO2, CO, and SO2 air sensor targets.

The use of air sensor technology is increasing worldwide for a variety of applications, however, with significant variability in data quality. The United States Environmental Protection Agency held a workshop in July 2019 to deliberate possible performance targets for air sensors measuring particles with aerodynamic diameters of 10 µm or less (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), and sulfur dioxide (SO2). These performance targets were discussed from the perspective of non-regulatory applications and with the sensors operating primarily in a stationary mode in outdoor environments. Attendees included representatives from multiple levels of government organizations, sensor developers, environmental nonprofits, international organizations, and academia. The workshop addressed the current lack of sensor technology requirements, discussed fit-for-purpose data quality needs, and debated transparency issues. This paper highlights the purpose and key outcomes of the workshop. While more information on performance and applications of sensors is available than in past years, the performance metrics, or parameters used to describe data quality, vary among the studies reports and there is a need for more clear and consistent approaches for evaluating sensor performance. Organizations worldwide are increasingly considering, or are in the process of developing, sensor performance targets and testing protocols. Workshop participants suggested that these new guidelines are highly desirable, would help improve data quality, and would give users more confidence in their data. Given the wide variety of uses for sensors and user backgrounds, as well as varied sensor design features (e.g., communication approaches, data tools, processing/adjustment algorithms and calibration procedures), the need for transparency was a key workshop theme. Suggestions for increasing transparency included documenting and sharing testing and performance data, detailing best practices, and sharing data processing and correction approaches.

[A comparative study on the difference of gut microbiota and its biomarkers between patients with pulmonary tuberculosis and healthy controls].

Objective: To analyze the differences in the composition and abundance of gut microbiota between patients with active pulmonary tuberculosis and healthy controls, and to identify the specific bacteria as biomarkers to distinguish between the two groups. Methods: Patients with active pulmonary tuberculosis treated in three municipal designated tuberculosis medical institutions in Sichuan, Jiangsu and Shanghai from September 2017 to September 2019 were selected as the case group (n=88), and the healthy people without a history of tuberculosis from the same regions were recruited as the control group (n=62). The fecal samples of the two groups were detected by 16S rRNA gene sequencing, and the differences of gut microbiota diversity, community composition and relative abundance at phylum and genus level from the two groups were analyzed. The random forest method was used to construct a predictive model to assess whether the specific bacterial flora could be used as biomarkers to distinguish tuberculosis patients from healthy people. Results: The alpha diversity analysis showed that the species richness and evenness of gut microbiota in tuberculosis patients were significantly lower than those in healthy controls (P<0.001). There was a statistically significant difference in the composition of microbiota between the two groups (Bray-Curtis distance, P<0.001). In the gut microbiota of tuberculosis patients, opportunistic pathogens were relatively enriched, while some of the beneficial bacteria that can produce short-chain fatty acids were less abundant. The discrimination accuracy of the random forest model composed of Lachnospira, Lachnospiraceae ND3007 group and Roseburia was 76.67%, with area under the curve (AUC) being 75.29% (95%CI: 0.661-0.845). Conclusion: There were differences in gut microbiota between patients with active pulmonary tuberculosis and healthy people, and specific bacterial flora showed the potential to be used as biomarkers to distinguish between the two groups.

[Cancer metabolism: a novel perspective on precision diagnosis and treatment for liver cancer].

Metabolic reprogramming has been identified as a hallmark of cancer. Liver is an essential hub in the body for the metabolism of three major nutrients including glucose, lipids and amino acids. Hepatocellular carcinoma(HCC) usually presents a variety of changes in characteristic metabolism, such as increased aerobic glycolysis, enhanced de novo lipid synthesis, glutamine depletion, and oxidative metabolism imbalance, which can provide energy and bio-macromolecular raw materials for rapidly growing and proliferating tumor cells. The process of tumor metabolic reprogramming is regulated by multiple factors, such as alterations in metabolic enzyme activity, abnormal gene expression, and signaling pathway disturbance. Advances in high-throughout metabolomics technology have provided a powerful platform for discovering the novel biomarkers and metabolic targets of HCC. Therefore, in-depth study of the metabolic characteristics and regulatory mechanisms of HCC is critical for the development of novel antimetabolites.

Genomic variation in Pekin duck populations developed in three different countries as revealed by whole-genome data.

It is well known that both British and American Pekin ducks originated from China. However, the populations differ substantially in production performance, but the genetic changes involved are still poorly understood. Herein, we sequenced 24 individual Pekin ducks (eight from each population) with an average sequencing depth of more than 45× for each population (mean coverage of 6.29 per individual). Among these populations from three different countries, we identified a large number of SNPs and indels as well as many unique population variants, which can be used as population-specific molecular markers. Genomic comparisons among the three duck populations revealed many candidate genes as well as pathways and Gene Ontology categories that are putatively associated with meat yield in the British population, growth in the American population and brain development in all three populations. These findings will enable a better understanding of the artificial selection history of Pekin ducks and provide a valuable resource for future research on the breeding of this species.

[Spatial-temporal analysis on the human immunodeficiency virus/acquired immunodeficiency syndrome among permanent residence and migrants in Shanghai, 2005-2015].

Objective: To describe the spatial and temporal characteristics of human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS) in permanent residents and migrants in Shanghai during 2005 to 2015 and provide suggestions for the HIV/AIDS prevention. Methods: The data of HIV/AIDS was collected from the National HIV/AIDS Comprehensive Information Management System based on report date. The population data was collected from the statistical yearbook of Shanghai. Spatial analysis was conducted using the hotspots model in ArcGIS. SaTScan software was employed to determine the distribution of HIV clusters in space, time or both. Results: During 2005 to 2015, a total of 13 498 cases of HIV/AIDS were reported in Shanghai. The prevalence of HIV increased from 0.025/10(5) (450 cases) to 0.093/10(5) (2 236 cases). The prevalence of AIDS increased from 0.002/10(5) (32 cases) to 0.028/10(5) (683 cases). Hotspot analysis showed that the hot spot of incidence of migrants had moved from Hongkou (2005) (Z=2.96, P=0.003) to Changning (2006-2015) (all Z>1.96, P<0.05); whereas the hot spot of incidence of permanent residents had moving from Jinshan (2005-2007) (all Z>2.58, P<0.01) to downtown area (2006-2015) (all Z>1.96, P<0.05). The spatial high clusters of HIV and AIDS were same, including Huangpu, Xuhui, Changning, Jingan, Putuo, Hongkou and Yangpu; The temporal high clusters of HIV cases among permanent residents were 2011 to 2015, and the spatial clusters were Huangpu, Xuhui, Changning, Jingan. The temporal high clusters of HIV cases among migrants were 2014 to 2015, and the spatial clusters was Xuhui, Changning, Jingan. Conclusion: The total HIV/AIDS incidence in Shanghai was clustered in downtown area. The cluster of the incidence of the permanent residents had moving towards that of migrants, indicating the cluster area deserves a close surveillance.

Vertebral fracture in postmenopausal Chinese women: a population-based study.

In a random sample of postmenopausal Chinese women, the prevalence of radiographic vertebral fractures increased from 13% between ages 50 and 59 to over 50% after age 80 years. A model with seven clinical risk factors predicted the probability of vertebral fractures as well with as without BMD and better than a model with only three risk factors. More than half an hour of outdoor activity per day might correlate with lower risk of vertebral fracture in this population. INTRODUCTION: We aimed to describe the prevalence and develop a model for prediction of radiographic vertebral fractures in a large random sample of postmenopausal Chinese women. METHODS: We enrolled 1760 women from an age-stratified random sample of postmenopausal women in Beijing, China. The presence of vertebral fracture was assessed by semi-quantitative grading of lateral thoracolumbar radiographs, risk factors by interview, bone mineral density (BMD) of the proximal femur and lumbar spine by dual x-ray absorptiometry (DXA), and markers of bone turnover from a fasting blood sample. Associations of these factors were analyzed in logistic models and discrimination by areas of receiver operating characteristics curves (AUC). RESULTS: The prevalence of vertebral fracture, ranged from 13.4% ages 50 to 59 years old to 58.1% at age 80 years or older. Older age, a history of non-vertebral fracture, lower femoral neck BMD T-score, body mass index (BMI), height loss, housework, and less than half an hour of outdoor activity were significantly associated with increased probability of having a vertebral fracture. A model with those seven factors had a similar AUC with or without BMD and performed better than a simple model with three factors. CONCLUSION: This study is from a true random sample of postmenopausal women in urban China with high response rate. The prevalence of vertebral fractures in postmenopausal women in Beijing increases from 13% under age 60 to over 50% by age 80 years. A model with seven clinical risk factors with or without BMD is better than simple models and may guide the use of spine x-rays to identify women with vertebral fractures. More than half an hour of outdoor activity might correlate with lower risk of vertebral fracture in this population.

Differential prevalence and correlates of whole blood Epstein-Barr virus DNA between HIV-positive and HIV-negative men who have sex with men in Shanghai, China.

This cross-sectional study aimed to examine and compare prevalence and correlates of whole blood Epstein-Barr virus (EBV) DNA between HIV-positive and HIV-negative men who have sex with men (MSM). Five hundred and four HIV-positive MSM and 504 age-matched HIV-negative MSM were recruited from an HIV counseling and testing clinic in Shanghai, China from November 2014 to November 2015 and were administered with a face-to-face questionnaire interview. Whole blood EBV DNA was tested by nested polymerase chain reaction assays on EBNA-1, EBNA-2, and LMP-1 genes. The prevalence of whole blood EBV DNA was 56·0% (95% CI 51·7-60·3%) among HIV-positive MSM and 26·0% (95% CI 22·4-30·0%) among HIV-negative MSM. Whole blood EBV DNA positivity was significantly associated with HIV infection (adjusted odds ratio (aOR) 3·43, 95% CI 2·58-4·57) and frequent intake of pickled, smoked, or salty food (aOR 1·71, 95% CI 1·02-2·86) in the whole sample, and with <200 cells/µl CD4 cell counts (aOR 1·79, 95% CI 1·05-3·05) and pickled, smoked, or salty food intake (aOR 3·14, 95% CI 1·39-7·08) in HIV-positive group. HIV-infected MSM are at higher risk of active EBV replication than HIV-uninfected MSM, underscoring needs of surveillance and research on EBV-related carcinogenesis in this population.

Effect of light-emitting diode vs. fluorescent lighting on laying hens in aviary hen houses: Part 1 - Operational characteristics of lights and production traits of hens.

Light-emitting diode (LED) lights are becoming more affordable for agricultural applications. Despite many lab-scale studies concerning impact of LED on poultry, little research has been documented under field production conditions, especially for laying hens. This 15-month field study was carried out to evaluate the effects of LED vs. fluorescent (FL) lights on laying hens (Dekalb white breed) using 4 (2 pairs) aviary hen houses each at a nominal capacity of 50,000 hens. The evaluation was done regarding operational characteristics of the lights and hen production traits. The results show that spatial distribution of the LED light was less uniform than that of the FL light. Light intensity of the LED light decreased by 27% after 3,360 h use but remained quite steady from 3,360 to 5,760 h use. Eleven out of 762 (1.44%) LED lamps (new at onset of the study) in the 2 houses failed during the 15-month experiment period. The neck area of the LED lamp was hottest, presumably the primary reason for the lamp failure as cracks were noticed in the neck region of all failed LED lamps. No differences were observed in egg weight, hen-day egg production, feed use, and mortality rate between LED and FL regimens. However, hens under the FL had higher eggs per hen housed and better feed conversion than those under the LED during 20 to 70 wk production (P < 0.05). Hens under the LED tended to have less feather uniformity and insulation than those under the FL (P < 0.05). Moreover, hens under the LED showed a larger median avoidance distance than those under the FL at 36 wk age (P < 0.05), indicating that hens under the LED were more alert; but no difference at 60 wk age. More comparative research to quantify behavioral and production responses of different breeds of hens to LED vs. FL lighting seems warranted.

Effect of light-emitting diode (LED) vs. fluorescent (FL) lighting on laying hens in aviary hen houses: Part 2 - Egg quality, shelf-life and lipid composition.

In this 60-wk study, egg quality, egg shelf-life, egg cholesterol content, total yolk lipids, and yolk fatty acid composition of eggs produced by Dekalb white laying hens in commercial aviary houses with either light-emitting diode (LED) or fluorescent (FL) lighting were compared. All parameters were measured at 27, 40, and 60 wk of age, except for egg shelf-life, which was compared at 50 wk of age. The results showed that, compared to the FL regimen, the LED regimen resulted in higher egg weight, albumen height, and albumen weight at 27 wk of age, thicker shells at 40 wk of age, but lower egg weight at 60 wk of age. Egg quality change was similar between the lighting regimens during the 62-d egg storage study, indicating that LED lighting did not influence egg shelf-life. Eggs from both lighting regimens had similar cholesterol content. However, cholesterol concentration of the yolk (15.9 to 21.0 mg cholesterol/g wet weight yolk) observed in this study was higher than that of United States Department of Agriculture (USDA) database (10.85 mg/g). No significant differences in total lipids or fatty acid composition of the yolks were detected between the two lighting regimens.

Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma.

BACKGROUND: Chidamide is a novel benzamide type of subtype-selective histone deacetylase (HDAC) inhibitor with unique mechanisms of action compared with marketed HDAC inhibitors. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL) in Chinese population. PATIENTS AND METHODS: Patients with relapsed or refractory PTCL of different subtypes received chidamide of 30 mg orally twice per week. The primary end point was overall response rate (ORR). Responding patients should be confirmed at least 4 weeks after the criteria of the response were first met, and were reviewed by an independent review committee. RESULTS: Eighty-three patients were enrolled and 79 patients with eligible PTCL histology were for efficacy assessments. Patients enrolled over 10% were with subtypes of PTCL not otherwise specified (34%), anaplastic large-cell lymphoma (22%), extranodal natural killer (NK)/T-cell lymphoma, nasal type (20%), or angioimmunoblastic T-cell lymphoma (AITL, 13%). The ORR was 28% (22 of 79) including 14% (11 of 79) with complete response/unconfirmed complete response (CR/CRu). Median progression-free survival and overall survival were 2.1 and 21.4 months, respectively. AITL patients tended to have higher ORR (50%) and CR/CRu rate (40%), as well as more durable responses, to chidamide treatment. Most adverse events (AEs) were grade 1 or 2, and AEs ≥grade 3 that occurred in ≥10% patients were thrombocytopenia (22%), leucopenia (13%) and neutropenia (11%), respectively. CONCLUSION: Chidamide represents a novel oral benzamide class of HDAC inhibitor with significant single-agent activity and manageable toxicity in relapsed or refractory PTCL, and provides a much needed treatment option in this indication in China. Results led to China Food and Drug Administration approval of chidamide in this indication.

Transversally and axially tunable carbon nanotube resonators in situ fabricated and studied inside a scanning electron microscope.

We report a new design of carbon nanotube (CNT) resonator, whose resonance frequency can be tuned not only transversally by a gate voltage, but also by the axial strain applied through directly pulling the CNT. The resonators are fabricated from individual suspended single-walled CNT (SWCNT) in situ inside a scanning electron microscope. The resonance frequency of a SWCNT resonator can be tuned by more than 20 times with an increase of quality factor when the axial strain of the SWCNT is only increased from nearly zero to 2% at room temperature. The transversal gate-tuning ability is found to be weaker than the axial-tuning ability and decrease with increasing the axial strain. The gate voltage can hardly tune the resonance frequency when the initial axial strain is larger than 0.35% and the CNT acts like a tied string. The relationship among resonance frequency, gate voltage, and initial axial strain of the CNT obtained presently will allow for the designs of CNT resonators with high frequency and large tuning range. The present resonator also shows ultrahigh sensitivity in displacement and force detection, with a resolution being better than 2.4 pm and 0.55 pN, respectively.

A platform for in-situ multi-probe electronic measurements and modification of nanodevices inside a transmission electron microscope.

We developed a new platform that enables in-situ four-probe electronic measurements, in-situ three-probe field-effect measurements, nanomanipulation, and in-situ modification of nanodevices inside a transmission electron microscope (TEM). The platform includes a specially designed chip-holder and a silicon (Si) chip with suspended metal electrodes. The chip-holder can hold one Si chip with a size up to 3 mm × 3 mm and provides four electrical connections that can be connected to the micrometer-sized electrodes on the Si chip by wire-bonding. The other side of the electrical connections on the chip-holder is connected to the electronic instruments outside the TEM through a commercial Nanofactory SPM-TEM holder. The Si chip with suspended metal electrodes on one of its edges was fabricated by lithography and wet etching. Carbon nanotubes (CNTs), InAs nanowires, and tungsten disulfide nanowires were placed to stride over and connect to the suspended electrodes on the Si chip by nanomanipulations inside a scanning electron microscope (SEM). By using the platform, I-V curves of an individual single-walled CNT connecting to four electrodes were in-situ measured between any two of the four suspended electrodes, and a high-resolution TEM image of the same CNT was obtained. Furthermore, four-terminal I-V measurement on an InAs nanowire was achieved on this platform, and with a movable probe used as a gate electrode, field-effect measurement on the same InAs nanowire device was accomplished in SEM. In addition, by using the movable probe on the SPM-TEM holder, we could further in-situ modify nanomaterial and nanodevices. The present work demonstrates a method that allows a direct correlation between the atomic-level structure and the electronic property of nanomaterials or nanodevices whose structure can be further modified in-situ.

In situ multiproperty measurements of individual nanomaterials in SEM and correlation with their atomic structures.

The relationship between property and structure is one of the most important fundamental questions in the field of nanomaterials and nanodevices. Understanding the multiproperties of a given nano-object also aids in the development of novel nanomaterials and nanodevices. In this paper, we develop for the first time a comprehensive platform for in situ multiproperty measurements of individual nanomaterials using a scanning electron microscope (SEM). Mechanical, electrical, electromechanical, optical, and photoelectronic properties of individual nanomaterials, with lengths that range from less than 200 nm to 20 µm, can be measured in situ with an SEM on the platform under precisely controlled single-axial strain and environment. An individual single-walled carbon nanotube (SWCNT) was measured on the platform. Three-terminal electronic measurements in a field effect transistor structure showed that the SWCNT was semiconducting and agreed with the structure characterization by transmission electron microscopy after the in situ measurements. Importantly, we observed a bandgap increase of this SWCNT with increasing axial strain, and for the first time, the experimental results quantitatively agree with theoretical predictions calculated using the chirality of the SWCNT. The vibration performance of the SWCNT, a double-walled CNT, and a triple-walled CNT were also studied as a function of axial strain, and were proved to be in good agreement with classical beam theory, although the CNTs only have one, two, or three atomic layers, respectively. Our platform has wide applications in correlating multiproperties of the same individual nanostructures with their atomic structures.

The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study.

BACKGROUND: H101, an innovative oncolytic adenovirus, has shown potential in modifying the tumor microenvironment from immunologically 'cold' to 'hot'. When combined with nivolumab, a programmed cell death protein 1 inhibitor, this synergy may offer substantial therapeutic benefits beyond the capabilities of each agent alone. PATIENTS AND METHODS: In this pilot study, we assessed the efficacy and safety of combining H101 with nivolumab in advanced hepatocellular carcinoma (HCC) patients who failed prior systemic therapy. The participants received initial oncolytic virus (OV) pretreatment with intratumoral H101 injections (5.0 × 1011 vp/0.5 ml/vial, two vials per lesion) on days 1 and 3. Combination therapy started on day 8, with H101 administered every 2 or 4 weeks and nivolumab (240 mg) injections every 2 weeks. Treatment continued up to 12 months or until disease progression, intolerable toxicity, consent withdrawal, or study conclusion. The primary endpoint was the objective response rate (ORR). RESULTS: Between March 2020 and March 2022, 18 of 21 screened patients were assessable, showing an ORR of 11.1% [two cases of partial response (PR) and five cases of stable disease], with extrahepatic injections often leading to favorable outcomes. The disease control rate stood at 38.9%, with a 6-month survival rate of 88.9%. Median progression-free survival was 2.69 months, and overall survival (OS) was 15.04 months. Common adverse events included low-grade fever (100%) and pain related to centesis (33.3%), and no grade 3/4 events were reported. Significantly, local H101 injection showed potential in reversing immune checkpoint inhibitor resistance, evidenced by over 2.5 years of extended OS in PR cases with low α-fetoprotein. Additionally, decreasing neutrophil-to-lymphocyte ratio during OV pretreatment may predict positive outcomes. CONCLUSIONS: This study demonstrates the potential efficacy of combining H101 with nivolumab in treating refractory advanced HCC, with well-tolerated toxicities.