A high-density and high-confinement tokamak plasma regime for fusion energy.

The tokamak approach, utilizing a toroidal magnetic field configuration to confine a hot plasma, is one of the most promising designs for developing reactors that can exploit nuclear fusion to generate electrical energy1,2. To reach the goal of an economical reactor, most tokamak reactor designs3-10 simultaneously require reaching a plasma line-averaged density above an empirical limit-the so-called Greenwald density11-and attaining an energy confinement quality better than the standard high-confinement mode12,13. However, such an operating regime has never been verified in experiments. In addition, a long-standing challenge in the high-confinement mode has been the compatibility between a high-performance core and avoiding large, transient edge perturbations that can cause very high heat loads on the plasma-facing-components in tokamaks. Here we report the demonstration of stable tokamak plasmas with a line-averaged density approximately 20% above the Greenwald density and an energy confinement quality of approximately 50% better than the standard high-confinement mode, which was realized by taking advantage of the enhanced suppression of turbulent transport granted by high density-gradients in the high-poloidal-beta scenario14,15. Furthermore, our experimental results show an integration of very low edge transient perturbations with the high normalized density and confinement core. The operating regime we report supports some critical requirements in many fusion reactor designs all over the world and opens a potential avenue to an operating point for producing economically attractive fusion energy.

A 0.6 Mpc H I structure associated with Stephan's Quintet.

Stephan's Quintet (SQ, co-moving radial distance = 85 ± 6 Mpc, taken from the NASA/IPAC Extragalactic Database (NED)1) is unique among compact groups of galaxies2-12. Observations have previously shown that interactions between multiple members, including a high-speed intruder galaxy currently colliding into the intragroup medium, have probably generated tidal debris in the form of multiple gaseous and stellar filaments6,8,13, the formation of tidal dwarfs7,14,15 and intragroup-medium starbursts16, as well as widespread intergalactic shocked gas5,10,11,17. The details and timing of the interactions and collisions remain poorly understood because of their multiple nature18,19. Here we report atomic hydrogen (H I) observations in the vicinity of SQ with a smoothed sensitivity of 1σ = 4.2 × 1016 cm-2 per channel (velocity bin-width Δv = 20 km s-1; angular resolution = 4'), which are about two orders of magnitude deeper than previous observations8,13,20,21. The data show a large H I structure (with linear scale of around 0.6 Mpc) encompassing an extended source of size approximately 0.4 Mpc associated with the debris field and a curved diffuse feature of length around 0.5 Mpc attached to the south edge of the extended source. The diffuse feature was probably produced by tidal interactions in early stages of the formation of SQ (>1 Gyr ago), although it is not clear how the low-density H I gas (NH i ≲ 1018 cm-2) can survive the ionization by the intergalactic ultraviolet background on such a long time scale. Our observations require a rethinking of properties of gas in outer parts of galaxy groups and demand complex modelling of different phases of the intragroup medium in simulations of group formation.

A dominant population of optically invisible massive galaxies in the early Universe.

Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light1. However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs2-4, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10-5 per cubic megaparsec (two orders of magnitude higher than extreme starbursts5) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.

Alfvénic velocity spikes and rotational flows in the near-Sun solar wind.

The prediction of a supersonic solar wind1 was first confirmed by spacecraft near Earth2,3 and later by spacecraft at heliocentric distances as small as 62 solar radii4. These missions showed that plasma accelerates as it emerges from the corona, aided by unidentified processes that transport energy outwards from the Sun before depositing it in the wind. Alfvénic fluctuations are a promising candidate for such a process because they are seen in the corona and solar wind and contain considerable energy5-7. Magnetic tension forces the corona to co-rotate with the Sun, but any residual rotation far from the Sun reported until now has been much smaller than the amplitude of waves and deflections from interacting wind streams8. Here we report observations of solar-wind plasma at heliocentric distances of about 35 solar radii9-11, well within the distance at which stream interactions become important. We find that Alfvén waves organize into structured velocity spikes with duration of up to minutes, which are associated with propagating S-like bends in the magnetic-field lines. We detect an increasing rotational component to the flow velocity of the solar wind around the Sun, peaking at 35 to 50 kilometres per second-considerably above the amplitude of the waves. These flows exceed classical velocity predictions of a few kilometres per second, challenging models of circulation in the corona and calling into question our understanding of how stars lose angular momentum and spin down as they age12-14.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

A machine learning model to predict therapeutic inertia in type 2 diabetes using electronic health record data.

OBJECTIVE: To estimate the therapeutic inertia prevalence for patients with type 2 diabetes, develop and validate a machine learning model predicting therapeutic inertia, and determine the added predictive value of area-level social determinants of health (SDOH). METHODS: This prognostic study with a retrospective cohort design used OneFlorida data (linked electronic health records (EHRs) from 1240 practices/clinics in Florida). The study cohort included adults (aged ≥ 18) with type 2 diabetes, HbA1C ≥ 7% (53 mmol/mol), ≥one ambulatory visit, and ≥one antihyperglycemic medication prescribed (excluded patients prescribed insulin before HbA1C). The outcome was therapeutic inertia, defined as absence of treatment intensification within six months after HbA1C ≥ 7% (53 mmol/mol). The predictors were patient, provider, and healthcare system factors. Machine learning methods included gradient boosting machines (GBM), random forests (RF), elastic net (EN), and least absolute shrinkage and selection operator (LASSO). The DeLong test compared the discriminative ability (represented by C-statistics) between models. RESULTS: The cohort included 31,087 patients with type 2 diabetes (mean age = 58.89 (SD = 13.27) years, 50.50% male, 58.89% White). The therapeutic inertia prevalence was 39.80% among the 68,445 records. GBM outperformed (C-statistic from testing sample = 0.84, 95% CI = 0.83-0.84) RF (C-statistic = 0.80, 95% CI = 0.79-0.80), EN (C-statistic = 0.80, 95% CI = 0.80-0.81), and LASSO (C-statistic = 0.80, 95% CI = 0.80-0.81), p < 0.05. Area-level SDOH significantly increased the discriminative ability versus models without SDOH (C-statistic for GBM = 0.84, 95% CI = 0.84-0.85 vs. 0.84, 95% CI = 0.83-0.84), p < 0.05. CONCLUSIONS: Using EHRs of patients with type 2 diabetes from a large state, machine learning predicted therapeutic inertia (prevalence = 40%). The model's ability to predict patients at high risk of therapeutic inertia is clinically applicable to diabetes care.

Racial/ethnic disparities in exposure to e-cigarette advertising among U.S. youth.

OBJECTIVES: This study aims to assess exposure to e-cigarette advertising across multiple marketing channels among U.S. youth and to examine whether racial/ethnic disparities exist in exposure to e-cigarette advertisements. STUDY DESIGN: This is a cross-sectional study. METHODS: Cross-sectional data were drawn from a longitudinal survey of participants recruited from two nationally representative panels (NORC's AmeriSpeak® and GfK's KnowledgePanel). A total of 2043 youth aged 13-17 completed the initial 2018 survey, and 2013 youth completed the follow-up survey in 2019 (including a replenishment sample of 690 youth). Outcome variables were self-reported e-cigarette advertisement exposure in the past three months through various sources, such as television, point of sale, and online/social media. Generalized estimating equation models were used to estimate the adjusted odds ratios (AOR) of the association between racial/ethnic identity and e-cigarette advertisement exposure. RESULTS: The prevalence of reported exposure to e-cigarette advertisements through any channel was 79.8% (95% CI: 77.1-82.2) in 2018 and 74.9% (95% CI: 72.5-77.1) in 2019, respectively. Point of sale was the most common source of e-cigarette advertisement exposure in both years. Non-Hispanic Black and non-Hispanic Asian youth were more likely to report exposure to e-cigarette advertisements through television (AOR = 2.07, 95% CI: 1.44-2.99 and AOR = 2.11, 95% CI: 1.17-3.82, respectively) and online/social media (AOR = 1.61; 95% CI: 1.11-2.33 and AOR = 1.99, 95% CI: 1.10-3.59, respectively) channels compared with non-Hispanic White youth. CONCLUSIONS: A substantial proportion of U.S. youth reported exposure to e-cigarette advertising through a variety of marketing channels. Significant racial/ethnic disparities existed, with non-Hispanic Black and Asian youth reporting more marketing exposure than their non-Hispanic White counterparts.

First Report of Root-knot Nematode, Meloidogyne enterolobii on Passiflora edulis in Yulin, China.

Passion fruit (Passiflora edulis), a medicinal plant, was introduced into China in the early 19th century, is mainly cultivated in southern provinces (Liang et al. 2019). During March 2023, a survey was carried out and 167 samples were taken from passion fruit cultivated area in Yulin (22.6570263°E; 110.1765019°N) apart from the planting base appeared yellow leaves, stunted growth, and distinctive galls on the roots. Within the galls, Meloidogyne sp. females and egg masses were observed. From the rhizosphere soil, second-stage juveniles (J2) were extracted, and population density was 105/500 g soil. The species was determined to be Meloidogyne enterolobii based on morphological characteristics, including female perineal pattern, and genetic analyses. Female (n = 10) perineal patterns showed oval shape, with coarse and smooth striae, dorsal arch rounded to square, and lateral lines not distinct. The male head cap was high and rounded, with the head region only slightly set off from the body, knobs large, ovoid to rounded. The measurements of males (n = 10) included body length, 1,230.7 ± 244.94 (997 to 1,569) µm; a, 38.58 ± 7.8 (33.45 to 47.05) µm; c, 113.03 ± 26.22 (80.82 to 144.23) µm; stylet, 15.68 ± 1.1 (14.5 to 17.4) µm; spicules, 31.83 ± 2.84 (28.69 to 36.1) µm; tail, 11.09 ± 1.72 (8.02 to 13.38) µm; and gubernaculum length, 8.34 ± 0.28 (8.11 to 8.98) µm. Measurements of J2 (n = 20) included body length, 455.75 ± 44.94 (381 to 512) µm; a, 26.32 ± 3.89 (18.18 to 32.70) µm; c, 8.56 ± 1.2 (6.36 to 10.80) µm; stylet, 12.44 ± 0.76 (11.2 to 13.8) µm; DGO, 3.65 ± 0.54 (2.84 to 4.68) µm; tail, 53.89 ± 6.36 (39.8 to 62.2) µm; and hyaline tail terminus, 11.77 ± 2.83 (7.14 to 16.2) µm. These morphological characteristics are similar to those reported in the original description of M. enterolobii (Yang and Eisenback 1983). The sequences of the partial ITS region was amplified with V5367 (5'-TTGATTACGTCCCTGCCCTTT-3') and 26S (5'-TTTCACTCGCCGTTACTAAGG-3') primers (Vrain et al. 1992). The region between cytochrome oxidase subunit II (COII) and the 16S rRNA mitochondrial DNA (mtDNA COII) was also amplified with the primers C2F3 (5'-GGTCAATGTTCAGAAATTTGTGG-3') (Powers and Harris 1993) and MRH106 (5'-AATTTCTAAAGACTTTTCTTAGT-3') (Stanton et al. 1997). The ITS region yielded a fragment of 757 bp (OR072957) and mtDNA COII of 706 bp (OR078415). A BLAST search indicated the sequences were 100% identical to several sequences of M. enterolobii (MT406250, MH756127 and AY831967, MN269940, respectively). To confirm pathogenicity, 20 passion fruit (P. edulis Sim. f. flavicarpa) 30-day-old seedlings were transplanted into pots with an autoclaved mixture of sand and field soil (3:1) and maintained in the glasshouse at 25 ± 2°C with 65 ± 5% relative humidity. After eight weeks, fifteen plants were inoculated with 500 J2/pot (nematode culture collected from the original field), and another five uninoculated plants served as a control. Two months later, aboveground symptoms were similar to those observed in the field. Nematode reproduction occurred and root galls were observed. The reproduction factor (nematode final population density/initial population density) was 4.8. The disease caused by M. enterolobii was severe in Yulin city of Guangxi. Guangxi is an important area for passion fruit culture, with about 2000 ha, which is responsible for two-thirds of China production (Xing et al. 2020). This is the first record of P. edulis natural infection with M. enterolobii in the Yulin City of Guangxi, China.

Dietary habits and physical activity during the third wave of the COVID-19 pandemic: associated factors, composite outcomes in a cross-sectional telephone survey of a Chinese population, and trend analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created many challenges for Hong Kong residents attempting to maintain healthy lifestyle habits. This study aimed to measure the prevalences of unhealthy dietary habits and physical inactivity levels in Hong Kong Chinese, identify associated factors, and conduct a time trend analysis during the third wave of the COVID-19 pandemic. METHODS: A cross-sectional telephone survey was conducted in Hong Kong by simple random sampling. The survey comprised socio-demographic characteristics, clinical information, the Hong Kong Diet Score (HKDS), smoking and alcohol consumption, and a Chinese version of the International Physical Activity Questionnaire Short Form. The composite outcome was low HKDS, physical inactivity, smoking, and alcohol consumption. We used 14 Health Behaviour Survey reports from 2003 to 2019 to establish a trend analysis regarding fruit and vegetable consumption, physical activity level, smoking, and alcohol consumption. RESULTS: We performed 1500 complete telephone surveys with a response rate of 58.8%. Most participants were older adults (≥65 years, 66.7%), women (65.6%), and married (77.9%). The HKDS was significantly lower in men, single individuals, low-income participants, alcohol drinkers, and patients with diabetes mellitus or renal disease. Participants who were single, undergoing long-term management of medical diseases, or had diabetes or renal diseases exhibited greater likelihood of physical inactivity. CONCLUSION: Prevalences of unhealthy lifestyle habits were high among men, single individuals, and chronic disease patients during the third wave of the COVID-19 pandemic in Hong Kong. The adoption of physical activity habits tended to decrease in the past two decades.

A prospective cohort study exploring the impact of tonsillectomy on feeding difficulties in children.

OBJECTIVES: Paediatric feeding difficulties are common, affecting up to 25% of otherwise healthy children, symptoms include food refusal, gagging, choking, and excessive mealtime duration. These symptoms are commonly described in pre-operative discussions about tonsillectomy. This prospective study explores the impact of tonsillectomy on paediatric feeding difficulties. DESIGN: This prospective cohort study invited caregivers of children undergoing tonsillectomy to complete a PediEAT questionnaire about their children's feeding behaviours, pre and post-operatively. The study was completed in two phases with 9 questions administered in phase 1 and three additional questions added for phase 2. A free text comments box was also provided. Responses were graded from 0 to 5, where 0 is 'never a problem' and 5 is 'always a problem' with eating behaviours. SETTING: The study was conducted at our institution, a tertiary paediatric ENT unit. PARTICIPANTS: Children aged between 6 months - 7 years undergoing tonsillectomy for any indication were invited to participate. MAIN OUTCOME MEASURES: Changes to the Pedi-EAT scores pre and post operatively were the main outcome measure. RESULTS: 102 participants were recruited between January 2020 and January 2022. The mean age of participants was 4.1 years, 87% had a concurrent adenoidectomy. The mean time to completion of post-operative questionnaire was 23 weeks after surgery. 9 of the 12 questions showed a statistically significant improvement in post-operative scores using a paired student t-test (p < 0.05). The most significant improvements related to 'gets tired from eating and is not able to finish' (1.49 pre-op, 0.91 post op, p < 0.01) and 'eats food that needs to be chewed' (1.4 pre-op, 0.72 post-op, p < 0.01). 13% of participants only underwent tonsillectomy and this group also showed a statistically significant improvement in fatigue during eating (p < 0.05). CONCLUSION: Symptoms of fatigue during eating and avoidance of food requiring mastication are most likely to improve following tonsillectomy in children.

[Analysis of clinical characteristics and risk factors of postoperative complications in infants with early-onset necrotizing enterocolitis after enterostomy].

Objective: To investigate the clinical characteristics of children with early-onset necrotizing enterocolitis (NEC) undergoing enterostomy and analyze the risk factors for postoperative complications. Methods: Retrospective analysis was conducted on the clinical data (perinatal conditions, clinical characteristics, clinical outcomes, etc.) of NEC patients who underwent enterostomy at Beijing Children's Hospital from May 2016 to May 2023. The patients were divided into two groups based on the age of onset: an early-onset enterostomy group (<14 days) and a late-onset enterostomy group (≥14 days). Furthermore, the children with NEC were categorized into complication group and non-complication group based on whether there were complications after enterostomy. The differences in clinical data between these groups were analyzed, and the clinical characteristics of children with early-onset NEC and enterostomy were summarized. Multivariate logistic regression model was employed to analyze the risk factors for postoperative complications in NEC children with enterostomy. Results: A total of 68 cases were enrolled, including 43 cases in the early-onset enterostomy group [26 males and 17 females, aged (6.5±3.0) days] and 25 cases in the late-onset enterostomy group [15 males and 10 females, aged (21.0±3.0) days]. There were 28 cases (17 males and 11 females), age [M (Q1, Q3)] 9 (5, 14) days in the complication group and 33 cases (22 males and 11 females), aged of 14 (6, 21) days in the non-complication group. Compared to the late-onset enterostomy group, the early-onset enterostomy group had significantly higher rates of intraventricular hemorrhage [30.2% (13/43) vs 8.0% (2/25)], hemodynamically significant patent ductus arteriosus [37.2% (16/43) vs 12.0% (3/25)], mechanical ventilation≥72 hours after birth [39.5% (17/43) vs 16.0% (4/25)], stage Ⅲ NEC [(69.8% (30/43) vs 40.0% (10/25)], extensive NEC [27.9% (12/43) vs 8.0% (2/25)], and short-term postoperative complications [56.8% (21/37) vs 29.2% (7/24)] (all P<0.05).Multivariate logistic regression model analysis revealed that residual length of proximal small intestine was a protective factor for postoperative complications after enterostomy in NEC infants (OR=0.764, 95%CI: 0.648-0.901, P=0.001), but stage Ⅲ NEC was a risk factor (OR=1.042, 95%CI: 1.004-5.585, P=0.017). Conclusions: The incidence of postoperative complications is high, and the prognosis is poor in children with early-onset NEC enterostomy. The residual length of proximal enterostomy is a protective factor for postoperative complications of NEC enterostomy, but stage Ⅲ NEC is a risk factor.

[Feasibility analysis of the application of programmed process endoscopic lateral neck dissection via chest-breast approach in papillary thyroid carcinoma surgery].

Objective: To explore the feasibility of endoscopic lymph node dissection(LND) with programmed breast approach for the treatment of papillary thyroid cancer. Methods: A case series study. The clinical data of 39 patients with papillary thyroid cancer who underwent endoscopic LND treatment with programmed breast approach in Shenzhen People's Hospital from January to November 2022 were retrospectively analyzed. There were 10 males and 29 females, aged (35.95±10.17) years. LND time, total surgical time, intraoperative bleeding volume, postoperative drainage volume, postoperative hospital stay and postoperative complications were analyzed. Results: Among 39 patients, there were 18 cases of unilateral thyroid cancer, 21 cases of bilateral thyroid cancer, 35 cases of unilateral LND, and 4 cases of bilateral LND. The maximum diameter of thyroid cancer lesions was (1.48±0.69) cm, and the maximum diameter of lymph node metastases was (1.63±0.58)cm. The operative time of unilateral neck dissection was (124.11±19.92) min (102-170 min), and the total operative time was (226.42±55.68) min (110-390 min). The number of lymph nodes cleaned was (32.40±10.44)(12-54), the number of metastasis and detection was 207/1 393. The postoperative drainage volume was (174.64±82.33) ml(41-350 ml). There were no neck hematomas, no skin burns or no shrugging disorders in the postoperative period. There were 7 cases of numbness and discomfort in neck skin sensation, which gradually relieved after half a year. Postoperative discharge time (4.77±1.94) d(3-15 d). Conclusion: It is safe and feasible to treat papillary thyroid cancer with endoscopic LND with programmed breast approach, which can improve surgical efficiency and clinical application value.

[The clinicopathological features of adult thyroid tumors with DICER1 mutation].

A total of 37 cases of thyroid tumors with pathological features suggestive of DICER1 gene mutation were selected to detect the DICER1 gene and BRAF gene using Sanger sequencing. A total of 10 patients (27.0%) exhibited DICER1 gene mutation all of whom were female with an age of [M(Q1, Q3)] 38.0 (30.5, 47.5) years. All patients had wild-type BRAFV600E gene. The ultrasound examination showed high-low echogenic well-demarcated intra-thyroidal nodules with abundant peripheral and internal blood flow signals in the DICER1 mutated thyroid tumor. The tumor was confined within the thyroid gland, with a diameter of (3.68±1.31) cm. The pathological features are as follows: the majority of tumors are encapsulated, which mainly composed of large follicles rich in colloid and some are small and micro follicles. The nucleus is round and deeply stained or slightly light stained, small to medium-sized, with occasional nuclear grooves and a lack of nuclear pseudoinclusion bodies within the nucleus. Immunohistochemical staining shows that Ki67 proliferation index of approximately 2%-10%. All cases were followed up for 11 to 18 months, and there was no recurrences or distant metastase. This study confirmed that the DICER1 gene mutation is mutually exclusive with the BRAFV600E gene mutation. The thyroid tumor with DICER1 mutation are in big size and are more common in young females with a good prognosis. Cases with the wild-type DICER1 gene may exhibit similar morphological features, and molecular testing is recommended. If somatic DICER1 mutation is confirmed, patients should undergo germline mutation testing to rule out DICER1 syndrome in order to define whether genetic counseling is necessary.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

[Research progress of long-chain non-coding RNA in lipid metabolism reprogramming in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the most common liver malignant tumor with complex pathogenesis and a poor prognosis. Metabolic reprogramming has been recognized as one of the important cancer markers, and the liver, as an important organ for lipid metabolism in the human body, plays an important role in the process of the occurrence and development of HCC. More and more evidence shows that long-chain non-coding RNA (lncRNA) can influence the lipid metabolism process by regulating key enzymes and transcription factors, as well as being involved in the occurrence and development of HCC. Therefore, explicating the mechanism of lncRNA in lipid metabolism reprogramming is conducive to providing new targets and strategies for the diagnosis and treatment and improving the prognosis of HCC patients. This article summarizes the latest research progress on the involvement of lncRNA in the reprogramming process of HCC lipid metabolism.

[Research progress of non-coding RNA-encoding polypeptides in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with rapid progression and a poor prognosis. More and more studies have shown that there are small open reading frames (sORFs) on the molecular sequences of a large number of non-coding RNAs (ncRNAs), which can encode conserved peptides that play an important role in controlling the occurrence and development of HCC. This article introduces the discovery, prediction, and validation methods of ncRNA-encoding polypeptides and reviews its research progress, with the aim of providing new targets and ideas for early-stage diagnosis, targeted therapy, and prognosis assessment of HCC.

[Advances in immunotherapy for pulmonary sarcomatoid carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated non-small cell lung cancer (NSCLC) that contains sarcomatoid components or sarcomatoid differentiation, and accounts for less than 1% of all lung tumors. Compared to other types of NSCLC, PSC has more invasive biological behavior, is prone to metastasis, and has a higher recurrence rate after early surgery. Its greater resistance to traditional treatments leads to a poorer prognosis compared to other NSCLCs. Immunotherapy offers the possibility of long-term survival for PSC patients.

[Clinical analysis of lung adenocarcinoma with epidermal growth factor receptor mutation transformed into sarcoma].

Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

[Analysis of the therapeutic effect of aspiration thrombectomy for early carotid stent thrombosis].

Objective: To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS). Methods: This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected. Results: The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions: Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.