Serosal overturning assisted endoscopic full-thickness mucosal resection of extraneous giant mass at the esophagogastric junction.

Key Clinical Message: Serosal overturning assisted endoscopic full-thickness mucosal resection was performed on the extraneous giant masses at the esophagogastric junction without complications. Abstract: It is difficult to perform endoscopic resection of masses at the gastroesophageal junction (GEJ). In particular, the extraneous giant masses surrounding the extraneous giant masses is infrequent. As one of the technologies of endoscopic resection, endoscopic full-thickness resection (EFTR) is generally applicable to the submucosal tumor of stomach, duodenum and colorectal that originate from the musculus propria and protrude to subserous or partial growth outside the luminal layer. Successful endoscopic repair of perforation is crucial in avoiding the need for surgical repair and preventing postoperative peritonitis, making it a key aspect of EFTR treatment. We report a 56-year-old woman who was admitted to our department complaining of 5-year history of masses of esophagogastric junction and 2-month history of feeling of gastric distension. Gastroscopy showed a 4 cm submucosal mass near the fundus of the stomach from the cardia. Computed tomography scan revealed submucosal lesions in esophagogastric junction, which was exogenous. We successfully performed Serosal overturning assisted endoscopic full-thickness mucosal resection on the extraneous giant masses at the esophagogastric junction without complications. The clinical symptoms were significantly improved within postoperative 1 month. There was no recurrence 8 months after the operation. Serosal overturning assisted EFTR is possibly an effective and minimally invasive method of extraneous giant masses at the esophagogastric junction.

Interfacial Wrinkling Structures Based on a Double Cross-Linking Strategy Enable a Dual-Mode Optical Information Encryption.

Surface wrinkling structures based on a bilayer system are widely employed in storing and encrypting specific optical information. However, constructing a stable wrinkling structure with high-level security remains an extensive challenge due to the delamination issue between the skin layer and the substrate. Herein, a double cross-linking strategy is introduced between a hydrogel layer doped with fluorescent molecules and polydimethylsiloxane to establish a stable interfacial wrinkling structure with dual-mode functionality, in which the light reflection of the wrinkles and fluorescence intensity of fluorescent molecules can be simultaneously regulated by the modulus ratio between the two layers. The spontaneous wrinkling structures with a physically unclonable function can enhance the photoluminescence emission intensity of the wrinkling area under ultraviolet radiation. Meanwhile, the skin layer constructed of acrylamide and acrylic acid copolymer protects the interfacial wrinkling patterns from the loss of a detailed structure for authentication due to external damage. The stable interfacial wrinkling structures with fluorescence can find potential applications in the fields of information storage and encryption.

Risk factors and prediction model for delayed bleeding after cold snare polypectomy: a retrospective study.

BACKGROUND: Delayed bleeding (DB) is a serious complication after cold snare polypectomy (CSP) for polyps in the colon. The present study aimed to investigate the incidence and risk factors of DB after CSP and to develop a risk-scoring model for predicting DB. METHODS: A retrospective study was conducted in four Chinese medical institutions. 10650 patients underwent CSP from June 2019 to May 2023. The study analyzed the rate of DB and extracted the general clinical information and polyp-related information of patients with postoperative DB. As a control, non-DB patients who received CSP at the same 4 hospitals were analyzed. A multivariate Cox regression analysis was performed to develop the prediction model. The model was further validated using a Kaplan-Meier log-rank analysis, receiver operating characteristic curve (ROC) plot and risk plot. RESULTS: In our study, we found a 0.24% rate of DB and the risk factors were history of hypertension, hyperlipidemia, antithrombotics use, antiplatelet use, anticoagulant use, abdominal operation, sigmoid colon lesion, hematoma, cold snare defect protrusion, polyp size, wound size, the grade of wound bleeding, and morphology of Ip. These factors were incorporated into the prediction model for DB after CSP. For 1, 3, and 5 days of bleeding, the AUC of the ROC curve was 0.912, 0.939, and 0.923, respectively. The Kaplan-Meier analysis indicated that the high-risk group had a significantly higher risk of DB than the low-risk group. CONCLUSIONS: This study screened the risk factors and established a prediction model of DB after CSP. The results may help preventing and reducing the DB rate after CSP of colorectal polyps.

Drug supply and assurance: a cross-sectional study of drug shortage monitoring varieties in China.

BACKGROUND: Drug shortage is a worldwide problem that seriously threatens public health. China released the most comprehensive list of key drug shortage monitoring varieties ever in 2022. We aim to analyze the attributes and characteristics of the medicines within the list to provide a reference for improving China's supply security of shortage drugs. METHODS: We used public data to extract information on drug types, dosage forms, indications, classification of clinical uses, whether they were included in medical catalogs such as the National Essential Drugs, and the number of drug and active pharmaceutical ingredient (API) manufacturers. A descriptive statistical analysis was used. RESULTS: Of the 980 drugs on the list, 99.59% were chemicals and 92.65% were injectables. Drugs for blood and hematopoietic organs, the cardiovascular system, and the digestive tract and metabolism ranked among the top three shortages. Verification of the medical catalogs showed that 90.41% of the drugs belonged to the national essential drugs, 95.10% were medicare drugs, 2.55% were volume-based procurement drugs, and 14.70% were for rare diseases, and 42.04% were for children. In terms of drug supply capacity, 21.33% of drug approvals are less than 10, and there were even 26 drugs for exclusive production, close to 90% of manufacturers need to purchase APIs from outside. Among the 256 APIs included in the list, 152 APIs had less than 10 manufacturers, and there were even 5 APIs produced by only one enterprise nationwide. CONCLUSIONS: The situation of drug shortages in China was severe and complex, with serious shortages of medicines adapted to basic medical and healthcare needs and clinically necessary medicines, and a need to improve the production capacity of drugs and the ability to supply APIs. We recommend strengthening drug monitoring and stockpiling and accelerating the approval of shortage drugs to improve drug supply security.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses.

BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.

A case report of neonatal incontinentia pigmenti complicated by severe cerebrovascular lesions in one of the male monozygotic twins.

Background: This article reports a case of neonatal incontinentia pigmenti onset in only one male monozygotic twin with characteristic skin lesions after birth followed by severe cerebrovascular lesions. Case presentation: A male infant, the first of monozygotic twins, was born with multiple yellow pustules all over his body, repeated new herpes at different sites during the course of the disease, aggravated by fusion, warty crusts, and hyperpigmentation; biopsy pathology suggested eosinophilic spongiform edema of the skin. Peripheral blood eosinophils were significantly elevated, and brain magnetic resonance imaging revealed diffuse multiple cystic and lamellar abnormal signal areas in the left frontal and parietal lobes. On day 30, the infant showed neurological symptoms, such as poor response and apnea, and an emergency cranial computed tomography scan revealed abnormal changes in the left cerebral hemisphere and bilateral cerebellum. After admission, he was given a potassium permanganate bath and topical mupirocin for 1 month, and the skin abnormalities improved. He was treated with mechanical ventilation and vasoactive drugs for 2 days after the cerebrovascular accident, and died the same day after the parents chose hospice care. No deletion variants or point mutations were detected in subsequent genetic tests, and chromosomal copy number variation tests revealed different degrees of chimeric duplications and deletions in different regions of chromosomes Y and 3. The parents were healthy, and his twin brother had normal growth and development with no abnormalities at multiple follow-up visits. Conclusion: Neonatal incontinentia pigmenti in only one male monozygotic twin is extremely rare and the genetic diagnosis is challenging. Awareness of the combined cerebrovascular lesions needs to be enhanced, and potential prevention and treatment methods need to be explored to improve the prognosis.

Physical Unclonable Functions with Hyperspectral Imaging System for Ultrafast Storage and Authentication Enabled by Random Structural Color Domains.

Physical unclonable function (PUF) is attractive in modern encryption technologies. Addressing the disadvantage of slow data storage/authentication in optical PUF is paramount for practical applications but remains an on-going challenge. Here, a highly efficient PUF strategy based on random structural color domains (SCDs) of cellulose nanocrystal (CNC) is proposed for the first time, combing with hyperspectral imaging system (HIS) for ultrafast storage and authentication. By controlling the growth and fusion behavior of the tactoids of CNC, the SCDs display an irregular and random distribution of colors, shapes, sizes, and reflectance spectra, which grant unique and inherent fingerprint-like characteristics that are non-duplicated. Based on images and spectra, these fingerprint features are used to develop two sets of PUF key generation methods, which can be respectively authenticated at the user-end and the manufacturer-front-end that achieving a high coding capacity of at least 22304. Notably, the use of HIS greatly shortens the time of key reading and generation (≈5 s for recording, 0.5-0.7 s for authentication). This new optical PUF labels can not only solve slow data storage and complicated authentication in optical PUF, but also impulse the development of CNC in industrial applications by reducing color uniformity requirement.

Trans-nuclease activity of Cas9 activated by DNA or RNA target binding.

Type V and type VI CRISPR-Cas systems have been shown to cleave nonspecific single-stranded DNA (ssDNA) or single-stranded RNA (ssRNA) in trans, but this has not been observed in type II CRISPR-Cas systems using single guide RNA. We show here that the type II CRISPR-Cas9 systems directed by CRISPR RNA and trans-activating CRISPR RNA dual RNAs show RuvC domain-dependent trans-cleavage activity for both ssDNA and ssRNA substrates. Cas9 possesses sequence preferences for trans-cleavage substrates, preferring to cleave T- or C-rich ssDNA substrates. We find that the trans-cleavage activity of Cas9 can be activated by target ssDNA, double-stranded DNA and ssRNA. The crystal structure of Cas9 in complex with guide RNA and target RNA provides a structural basis for the binding of target RNA to activate Cas9. Based on the trans-cleavage activity of Cas9 and nucleic acid amplification technology, we develop the nucleic acid detection platforms DNA-activated Cas9 detection and RNA-activated Cas9 detection, which are capable of detecting DNA and RNA samples with high sensitivity and specificity.

Engineered Imine Reductase for Asymmetric Synthesis of Dextromethorphan Key Intermediate.

(S)-1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline ((S)-1-(4-methoxybenzyl)-OHIQ) is the key intermediate of the nonopioid antitussive dextromethorphan. In this study, (S)-IR61-V69Y/P123A/W179G/F182I/L212V (M4) was identified with a 766-fold improvement in catalytic efficiency compared with wide-type IR61 through enzyme engineering. M4 could completely convert 200 mM of 1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinoline into (S)-1-(4-methoxybenzyl)-OHIQ in 77% isolated yield, with >99% enantiomeric excess and a high space-time yield of 542 g L-1 day-1, demonstrating a great potential for the synthesis of dextromethorphan intermediate in industrial applications.

Photothermal-responsive lignin-based polyurethane with mechanically robust, fast self-healing, solid-state plasticity and shape-memory performance.

In light of the depletion of petrochemical resources and increase in environmental pollution, there has been a significant focus on utilizing natural biomass, specifically lignin, to develop sustainable and functional materials. This research presents the development of a lignin-based polyurethane (DLPU) with photothermal-responsiveness by incorporating lignin and oxime-carbamate bonds into polyurethane network. The abundant hydrogen bonds between lignin and the polyurethane matrix, along with its cross-linked structure, contribute to DLPU's excellent mechanical strength (30.2 MPa) and toughness (118.7 MJ·m-3). Moreover, the excellent photothermal conversion ability of DLPU (54.4 %) activates dynamic reversible behavior of oxime-carbamate bonds and hydrogen bonds, thereby endowing DLPU with exceptional self-healing performance. After 15 min of near-infrared irradiation, DLPU achieves self-healing efficiencies of 96.0 % for tensile strength and 96.3 % for elongation at break. Additionally, DLPU exhibits photocontrolled solid-state plasticity as well as an excellent phototriggered shape-memory effect (70 s), with shape fixity and recovery ratios reaching 98.8 % and 95.3 %, respectively. By exploiting the spatial controllability and photothermal-responsiveness of DLPU, we demonstrate multi-dimensional responsive materials with self-healing and shape-shifting properties. This work not only promotes the development of multi-functional polyurethanes but also provides a pathway for the high-value utilization of lignin.

Alkali injury-induced pathological lymphangiogenesis in the iris facilitates the infiltration of T cells and ocular inflammation.

Inflammatory lymphangiogenesis is intimately linked to immune regulation and tissue homeostasis. However, current evidence has suggested that classic lymphatic vessels are physiologically absent in intraocular structures. Here, we show that neolymphatic vessels were induced in the iris after corneal alkali injury (CAI) in a VEGFR3-dependent manner. Cre-loxP-based lineage tracing revealed that these lymphatic endothelial cells (LECs) originate from existing Prox1+ lymphatic vessels. Notably, the ablation of iridial lymphangiogenesis via conditional deletion of VEGFR3 alleviated the ocular inflammatory response and pathological T cell infiltration. Our findings demonstrate that iridial neolymphatics actively participate in pathological immune responses following injury and suggest intraocular lymphangiogenesis as a valuable therapeutic target for the treatment of ocular inflammation.

Assessment of the implementation of accelerated drug marketing registration procedures for antineoplastic and immunomodulating agents in China: based on 2016-2022 review data.

Objective: Since 2016, China has successively implemented Accelerated Drug Marketing Registration Procedures (ADMRPs) for drugs, including Breakthrough Therapy Drug (BTD), Conditional Approval (CA), and Priority Review and Approval (PRA), which have played an important role in promoting the development and review of clinically urgently needed drugs. In this study, we focused on the antineoplastic and immunomodulating agents approved for marketing through ADMRPs, to provide a reference for promoting the formation of a stable and mature regulatory system for the review and approval of antineoplastic drugs and immunomodulating agents in China. Methods: Reviewed the National Medical Products Administration (NMPA) drug review reports for the years 2016-2022 and screened the antineoplastic and immunomodulating agents approved through ADMRPs. Then, with the help of the NMPA website and the Yaozhi Database, two researchers independently queried and entered the detailed information of the selected drugs, and checked with each other. The attribute classification and main characteristics of the drugs were then analyzed with descriptive statistics to obtain the trend of drug types, drug review and approval status, and timeliness. Results: A total of 206 antineoplastic and immunomodulating agents were approved for marketing through five accelerated marketing registration procedures (or procedure combinations), with the average review time shortened by about 81 days. Among them, imported drugs accounted for a larger proportion, the most drugs for treating non-small cell lung cancer and lymphoma, and the largest number of PD-1/PDL-1 inhibitors, but pediatric drugs and rare disease drugs accounted for a smaller proportion. Conclusion: ADMRPs can promote the accessibility of antineoplastic and immunomodulating agents in China and safeguard the life and health rights of more patients. Nevertheless, it is necessary to pay attention to the expansion of the types of indications for medicines and to increase the development of drugs that are urgently needed by a small number of patients.

Robust, Ultrafast and Reversible Photoswitching in Bulk Polymers Enabled by Octupolar Molecule Design.

Improving the photoswitching rate and robustness of photochromic molecules in bulk solids is paramount for practical applications but remains an on-going challenge. Here, we introduce an octupolar design paradigm to develop a new family of visible light organic photoswitches, namely multi-branched octupolar Stenhouse Adducts (MOPSAs) featuring a C3-symmetrical A3-(D-core) architecture with a dipolar donor-acceptor (D-A) photochrome in each branch. Our design couples multi-dimensional geometric and electronic effects of MOPSAs to enable robust ultrafast reversible photoswitching in bulk polymers. Specifically, the optimal MOPSA (4 wt %) in commercial polyurethane films accomplishes nearly 100 % discoloration in 6 s under visible light with ∼ 100 % thermal-recovery in 17.4 s at 60 °C, while the acquired kinetics constants are 3∼7 times that of dipolar DASA counterpart and 1∼2 orders of magnitude higher than those of reported DASAs in polymers. Importantly, the MOPSA-doped polymer films sustain 500 discoloration/recovery cycles with slow degradation, superior to the existing DASAs in polymers (≤30 cycles). We discover that multi-dipolar coupling in MOPSA enables enhanced polarization and electron delocalization, promoting the rate-determining thermal cyclization, while the branched and non-planar geometry of MOPSA induces large free volume to facilitate the isomerization. This design can be extended to develop spiropyran or azobenzene-based ultrafast photochromic films. The superior photoswitching performance of MOPSAs together with their high-yield and scalable synthesis and facile film processing inspires us to explore their versatile uses as smart inks or labels for time-temperature indicators, optical logic encryption and multi-levelled data encryption.

Development and validation of a deep learning signature for predicting lymphovascular invasion and survival outcomes in clinical stage IA lung adenocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The presence of lymphovascular invasion (LVI) influences the management and outcomes of patients with clinical stage IA lung adenocarcinoma. The objective was the development of a deep learning (DL) signature for the prediction of LVI and stratification of prognosis. METHODS: A total of 2077 patients from three centers were retrospectively enrolled and divided into a training set (n = 1515), an internal validation set (n = 381), and an external set (n = 181). A -three-dimensional residual neural network was used to extract the DL signature and three models, namely, the clinical, DL, and combined models, were developed. Diagnostic efficiency was assessed by ROC curves and AUC values. Kaplan-Meier curves and Cox proportional hazards regression analyses were conducted to evaluate links between various factors and disease-free survival. RESULTS: The DL model could effectively predict LVI, shown by AUC values of 0.72 (95 %CI: 0.68-0.76) and 0.63 (0.54-0.73) in the internal and external validation sets, respectively. The incorporation of DL signature and clinical-radiological factors increased the AUC to 0.74 (0.71-0.78) and 0.77 (0.70-0.84) in comparison with the DL and clinical models (AUC of 0.71 [0.68-0.75], 0.71 [0.61-0.81]) in the internal and external validation sets, respectively. Pathologic LVI, LVI predicted by both DL and combined models were associated with unfavorable prognosis (all p < 0.05). CONCLUSION: The effectiveness of the DL signature in the diagnosis of LVI and prognosis prediction in patients with clinical stage IA lung adenocarcinoma was demonstrated. These findings suggest the potential of the model in clinical decision-making.

Different Microeukaryotic Trophic Groups Show Different Latitudinal Spatial Scale Dependences in Assembly Processes across the Continental Shelves of China.

The relative role of stochasticity versus determinism is critically dependent on the spatial scale over which communities are studied. However, only a few studies have attempted to reveal how spatial scales influence the balance of different assembly processes. In this study, we investigated the latitudinal spatial scale dependences in assembly processes of microeukaryotic communities in surface water and sediment along the continental shelves of China. It was hypothesized that different microeukaryotic trophic groups (i.e., autotroph, heterotroph, mixotroph, and parasite) showed different latitudinal scale dependences in their assembly processes. Our results disclosed that the relative importance of different assembly processes depended on a latitudinal space scale for planktonic microeukaryotes. In surface water, as latitudinal difference increased, the relative contributions of homogenous selection and homogenizing dispersal decreased for the entire community, while those of heterogeneous selection and drift increased. The planktonic autotrophic and heterotrophic groups shifted from stochasticity-dominated processes to heterogeneous selection as latitudinal differences surpassed thresholds of 8° and 16°, respectively. For mixotrophic and parasitic groups, however, the assembly processes were always dominated by drift across different spatial scales. The balance of different assembly processes for the autotrophic group was mainly driven by temperature, whereas that of the heterotrophic group was driven by salinity and geographical distance. In sediment, neither the entire microeukaryotic community nor the four trophic groups showed remarkable spatial scale dependences in assembly processes; they were always overwhelmingly dominated by the drift. This work provides a deeper understanding of the distribution mechanisms of microeukaryotes along the continental shelves of China from the perspective of trophic groups.

Structural and mechanistic insights into ribosomal ITS2 RNA processing by nuclease-kinase machinery.

Precursor ribosomal RNA (pre-rRNA) processing is a key step in ribosome biosynthesis and involves numerous RNases. A HEPN (higher eukaryote and prokaryote nucleotide binding) nuclease Las1 and a polynucleotide kinase Grc3 assemble into a tetramerase responsible for rRNA maturation. Here, we report the structures of full-length Saccharomyces cerevisiae and Cyberlindnera jadinii Las1-Grc3 complexes, and C. jadinii Las1. The Las1-Grc3 structures show that the central coiled-coil domain of Las1 facilitates pre-rRNA binding and cleavage, while the Grc3 C-terminal loop motif directly binds to the HEPN active center of Las1 and regulates pre-rRNA cleavage. Structural comparison between Las1 and Las1-Grc3 complex exhibits that Grc3 binding induces conformational rearrangements of catalytic residues associated with HEPN nuclease activation. Biochemical assays identify that Las1 processes pre-rRNA at the two specific sites (C2 and C2'), which greatly facilitates rRNA maturation. Our structures and specific pre-rRNA cleavage findings provide crucial insights into the mechanism and pathway of pre-rRNA processing in ribosome biosynthesis.

A CT-based deep learning model: visceral pleural invasion and survival prediction in clinical stage IA lung adenocarcinoma.

Pathologic visceral pleural invasion (VPI) in patients with early-stage lung cancer can result in the upstaging of T1 to T2, in addition to having implications for surgical resection and prognostic outcomes. This study was designed with the goal of establishing and validating a CT-based deep learning (DL) model capable of predicting VPI status and stratifying patients based on their prognostic outcomes. In total, 2077 patients from three centers with pathologically confirmed clinical stage IA lung adenocarcinoma were enrolled. DL signatures were extracted with a 3D residual neural network. DL model was able to effectively predict VPI status. VPI predicted by the DL models, as well as pathologic VPI, was associated with shorter disease-free survival. The established deep learning signature provides a tool capable of aiding the accurate prediction of VPI in patients with clinical stage IA lung adenocarcinoma, thus enabling prognostic stratification.