The safety and efficacy of the fissure-first approach in lung segmentectomy for patients with incomplete fissures.

Background: Lung segmentectomy has gained much more attention as an important surgical method for treating early-stage lung cancer. However, incomplete fissures increase the difficulty of lung segmentectomy. The aim of this study was to analyze the safety and efficacy of the fissure-first approach in precision resection of lung segments for patients with incomplete fissures. Methods: The clinical data of patients with incomplete fissures who underwent lung segmentectomy were retrospectively analyzed. Date was divided into fissure-first approach in lung segmentectomy group (group A) and fissure-last approach in lung segmentectomy group (group B). The general linear data, operation times, intraoperative adverse events, postoperative recovery dates and complications were compared. Results: A total of 122 patients with complete clinical data were included. Patients in group B had more COPD (p < 0.05), and the lesions in group A were more closely related to the hilum of the lung (p < 0.05). Compared to Group B, Group A achieved better surgical outcomes, such as operation time, postoperative hospital stays, intraoperative bleeding, number of intrapulmonary lymph nodes sampled, counts of resected subsegments (except the upper lobe of the right lung), and rate of conversion to thoracotomy (all p < 0.05). Conclusion: The fissure-first approach is a safe and effective surgical approach in lung segmentectomy for patients with incomplete fissures. This approach can reduce the counts of resected subsegments and improve techniques in lung segmentectomy for patients with lung incomplete fissures.

DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells.

Epithelial barrier dysfunction and crypt destruction are hallmarks of inflammatory bowel disease (IBD). Intestinal stem cells (ISCs) residing in the crypts play a crucial role in the continuous self-renewal and rapid recovery of intestinal epithelial cells (IECs). However, how ISCs are dysregulated in IBD remains poorly understood. Here, we observe reduced DHX9 protein levels in IBD patients, and mice with conditional DHX9 depletion in the intestinal epithelium (Dhx9ΔIEC) exhibit an increased susceptibility to experimental colitis. Notably, Dhx9ΔIEC mice display a significant reduction in the numbers of ISCs and Paneth cells. Further investigation using ISC-specific or Paneth cell-specific Dhx9-deficient mice demonstrates the involvement of ISC-expressed DHX9 in maintaining epithelial homeostasis. Mechanistically, DHX9 deficiency leads to abnormal R-loop accumulation, resulting in genomic instability and the cGAS-STING-mediated inflammatory response, which together impair ISC function and contribute to the pathogenesis of IBD. Collectively, our findings highlight R-loop-mediated genomic instability in ISCs as a risk factor in IBD.

d-type peptides based fluorescent probes for "turn on" sensing of heparin.

Developing "turn on" fluorescent probes was desirable for the detection of the effective anticoagulant agent heparin in clinical applications. Through combining the aggregation induced emission (AIE) fluorogen tetraphenylethene (TPE) and heparin specific binding peptide AG73, the promising "turn on" fluorescent probe TPE-1 has been developed. Nevertheless, although TPE-1 could achieve the sensitive and selective detection of heparin, the low proteolytic stability and undesirable poor solubility may limit its widespread applications. In this study, seven TPE-1 derived fluorescent probes were rationally designed, efficiently synthesized and evaluated. The stability and water solubility were systematically estimated. Especially, to achieve real-time monitoring of proteolytic stability, the novel Abz/Dnp-based "turn on" probes that employ the internally quenched fluorescent (IQF) mechanism were designed and synthesized. Moreover, the detection ability of synthetic fluorescent probes for heparin were systematically evaluated. Importantly, the performance of d-type peptide fluorescent probe XH-6 indicated that d-type amino acid substitutions could significantly improve the proteolytic stability without compromising its ability of heparin sensing, and attaching solubilizing tag 2-(2-aminoethoxy) ethoxy) acid (AEEA) could greatly enhance the solubility. Collectively, this study not only established practical strategies to improve both the water solubility and proteolytic stability of "turn on" fluorescent probes for heparin sensing, but also provided valuable references for the subsequent development of enzymatic hydrolysis-resistant d-type peptides based fluorescent probes.

Tobacco Quitline Callers Who Use Cannabis and Their Likelihood of Quitting Cigarette Smoking.

INTRODUCTION: Cigarette smoking continues to decline in the U.S., but cannabis use is increasing. Many people who smoke cigarettes also use cannabis. This study examines the characteristics of persons who co-use and those who do not co-use and the likelihood of quitting cigarettes for callers to Kick It California, a large state tobacco quitline. METHODS: Data were examined from Kick It California callers from January 2020 through December 2023 (N=45,151), including those from a subgroup randomly sampled and reached for evaluation at 7 months after quitline enrollment (n=3,545). The rate of cigarette smoking cessation at 7 months after enrollment for people who co-use cannabis was compared with that for people who do not. Analyses started in 2023 and concluded in January 2024. RESULTS: More than a quarter (27.2%) of Kick It California callers co-used cannabis. They were more likely to be male, to be younger, and to have a mental health condition than those who did not. Those who co-use cannabis and those who do not have similar rates of receiving quitline counseling or using Food and Drug Administration-approved cessation aids. Controlled for effects of personal characteristics and use of smoking-cessation services, people who co-use cannabis were less likely to quit cigarette smoking 7 months after enrollment (23.2% vs 28.9%; p<0.001). Among those who co-use, 42.9% intended to quit using cannabis in the next 30 days. CONCLUSIONS: A substantial percentage of tobacco quitline callers use cannabis. Those who do co-use quit cigarette smoking at a lower rate than those who do not. Over 40% of people who co-use reported intention to quit cannabis, making tobacco quitlines a rich environment to learn about people who co-use and develop strategies for intervention.

Acetylcholine triggered enzymatic cascade reaction based on Fe7S8 nanoflakes catalysis for organophosphorus pesticides visual detection.

BACKGROUND: Organophosphorus pesticides (OPs) play important roles in the natural environment, agricultural fields, and biological prevention. The development of OPs detection has gradually become an effective strategy to avoid the dangers of pesticides abuse and solve the severe environmental and health problems in humans. Although conventional assays for OPs analysis such as the bulky instrument required analytical methods have been well-developed, it still remains the limitation of inconvenient, inefficient and lab-dependence analysis in real samples. Hence, there is an urgent demand to develop efficient detection methods for OPs analysis in real scenarios. RESULTS: Here, by virtue of the highly efficient catalytic performance in Fe7S8 nanoflakes (Fe7S8 NFs), we propose an OPs detection method that rationally integrated Fe7S8 NFs into the acetylcholine (ACh) triggered enzymatic cascade reaction (ATECR) for proceeding better detection performances. In this method, OPs serve as the enzyme inhibitors for inhibiting ATECR among ACh, acetylcholinesterase (AChE), and choline oxidase (CHO), then reduce the generation of H2O2 to suppress the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) that catalyzed by Fe7S8 NFs. Benefiting from the integration of Fe7S8 NFs and ATECR, it enables a sensitive detection for OPs (e.g. dimethoate). The proposed method has presented good linear ranges of OPs detection ranging from 0.1 to 10 µg mL-1. Compared to the other methods, the comparable limits of detection (LOD) of OPs are as low as 0.05 µg mL-1. SIGNIFICANCE: Furthermore, the proposed method has also achieved a favorable visual detection performance of revealing OPs analysis in real samples. The visual signals of OPs can be transformed into RGB values and gathered by using smartphones, indicating the great potential in simple, sensitive, instrument-free and on-site analysis of pesticide residues in environmental monitoring and biosecurity research.

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1.

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Discovery of sesquiterpene from Youngia japonica with antitumor effect.

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.

The Influence of Thermal Parameters on the Self-Nucleation Behavior of Polyphenylene Sulfide (PPS) during Secondary Thermoforming.

During the secondary thermoforming of carbon fiber-reinforced polyphenylene sulfide (CF/PPS) composites, a vital material for the aerospace field, varied thermal parameters profoundly influence the crystallization behavior of the PPS matrix. Notably, PPS exhibits a distinctive self-nucleation (SN) behavior during repeated thermal cycles. This behavior not only affects its crystallization but also impacts the processing and mechanical properties of PPS and CF/PPS composites. In this article, the effects of various parameters on the SN and non-isothermal crystallization behavior of PPS during two thermal cycles were systematically investigated by differential scanning calorimetry. It was found that the SN behavior was not affected by the cooling rate in the second thermal cycle. Furthermore, the lamellar annealing resulting from the heating process in both thermal cycles affected the temperature range for forming the special SN domain, because of the refined lamellar structure, and expelled various defects. Finally, this study indicated that to control the strong melt memory effect in the first thermal cycle, both the heating rate and processing melt temperature need to be controlled simultaneously. This work reveals that through collaborative control of these parameters, the crystalline morphology, crystallization temperature and crystallization rate in two thermal cycles are controlled. Furthermore, it presents a new perspective for controlling the crystallization behavior of the thermoplastic composite matrix during the secondary thermoforming process.

Hospital-Initiated Smoking Cessation Among Patients Admitted with Behavioral Health Conditions.

BACKGROUND: Smoking rates among people living with behavioral health conditions (BHC) range from 30 to 65% and are 2-4 times higher than rates found in the general population. Starting tobacco treatment during a hospital stay is effective for smoking cessation, but little is known regarding treatment response among inpatients with BHC. OBJECTIVE: This study pooled data across multiple clinical trials to determine the relative success in quitting among participants with BHC compared to other study participants. PARTICIPANTS: Adults who smoke (≥ 18 years old) from five hospital-based smoking cessation randomized clinical trials. DESIGN: A retrospective analysis using data from the electronic health record to identify participants with primary diagnoses related to BHC. Recruitment and data analysis were conducted from 2011 to 2016. We used propensity score matching to pair patients with BHC to those with similar characteristics and logistic regression to determine differences between groups. MEASURES: The main outcome was self-reported 30-day abstinence 6 months post-discharge. RESULTS: Of 6612 participants, 798 patients had a BHC-related primary diagnosis. The matched sample included 642 pairs. Nearly 1 in 3 reported using tobacco medications after hospitalization, with no significant difference between patients with and without BHC (29.3% vs. 31.5%; OR (95% CI) = 0.90 (0.71, 1.14), p = 0.40). Nearly 1 in 5 patients with BHC reported abstinence at 6 months; however, their odds of abstinence were 30% lower than among people without BHC (OR (95% CI) = 0.70 (0.53,0.92), p = 0.01). CONCLUSION: When offered tobacco treatment, hospitalized patients with BHC were as likely as people without BHC to accept and engage in treatment. However, patients with BHC were less likely to report abstinence compared to those without BHC. Hospitals are a feasible and promising venue for tobacco treatment among inpatients with BHC. More studies are needed to identify treatment approaches that help people with BHC achieve long-term abstinence.

Development of a Natural Language Processing System to Identify Clinical Documentation of Electronic Cigarette Use.

Electronic Nicotine Delivery Systems (ENDS) use has increased substantially in the United States since 2010. To date, there is limited evidence regarding the nature and extent of ENDS documentation in the clinical note. In this work we investigate the effectiveness of different approaches to identify a patient's documented ENDS use. We report on the development and validation of a natural language processing system to identify patients with explicit documentation of ENDS using a large national cohort of patients at the United States Department of Veterans Affairs.

Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition.

The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

LGBTQ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behavior, 2010-2022.

INTRODUCTION: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes. AIMS AND METHODS: Californians (N = 333 429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n = 19 431) was followed up at seven months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban). RESULTS: Overall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's < .001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly three sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p = .263). Similar patterns were seen in urban and rural subgroups. CONCLUSIONS: LGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live. IMPLICATIONS: This study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.

Challenging Diagnosis: Unmasking the Enigma of Imaging Findings with Lung Schwannomas.

Schwannomas are benign slow-growing tumors arising from the embryonic neural crest cells of the nerve sheaths of peripheral and cranial nerves, and they are a rare type of soft tissue mass that is usually always solitary. Generally, it grows in the head, neck, and flexor portions of the limbs, where many nerves are located. Schwannomas of the lung are extremely rare. Fewer than ten cases of schwannomas in this organ region have been reported in the existing literature. In this case report, a 40-year-old male non-smoker was hospitalized with occasional chest pain. His chest computed tomographic scan revealed a 3.8 cm space occupying lesion in the upper lobe of the right lung. This lesion has clear boundaries and uneven internal density. And it was concluded as a benign lesion possibility, it is preferred to be considered as a haematoma. This space occupying lesion was eventually confirmed as a schwannoma by needle biopsy tissues. Due to the presence in rare locations, such as the lung, the clinical presentation of this space occupying lesion is non-specific, making diagnosis difficult. The data presented in this case report can help clinicians to obtain information on the identification of this disease, which highlighted lung schwannoma as a differential diagnosis for patients with intermittent pain. It can also alert clinicians and radiologists to observe every detail of the radiology imaging findings.

Building bridges of excellence: a comprehensive competence framework for nurses in hospice and palliative care-a mixed method study.

BACKGROUND: Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. METHODS: This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. RESULTS: The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. CONCLUSIONS: The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses' development.

Long scleral tunnel technique for prevention of drainage tube-related complications during Ahmed glaucoma valve implantation.

To evaluate the safety and efficacy of modified Ahmed glaucoma valve (AGV) implantation (long scleral tunnel technique) in the treatment of neovascularization glaucoma (NVG). This retrospective observational case series included 23 patients (23 eyes) diagnosed with NVG secondary to proliferative diabetic retinopathy from January 2020 to June 2021. All 23 cases received anti-vascular endothelial growth factor treatment. Then, after 3 to 7 days, these cases were treated with modified AGV implantation (long scleral tunnel technique) and were followed up for at least 6 months. The best corrected visual acuity, intraocular pressure, numbers of antiglaucoma medications used, and postoperative complications were observed at 1 week and 1, 3, and 6 months after treatment. With treatment, the mean best corrected visual acuity improved significantly (P < .001) from 1.62 ±â€…0.52 logMAR preoperatively to 1.29 ±â€…0.36 logMAR at the 6-month follow-up. The mean postoperative intraocular pressure was significantly lower than that before modified AGV implantation during follow-up period, decreasing from 45.48 ±â€…7.86 mm Hg preoperatively to 14.87 ±â€…1.96 mm Hg at 1 week, 18.39 ±â€…2.25 mm Hg at 1 month, 16.61 ±â€…1.47 mm Hg at 3 months, and 17.48 ±â€…1.38 mm Hg at 6 months (F = 256.646, P < .001). The median number of antiglaucoma medications used by patients also significantly decreased from 3 (3-4) preoperatively to 0 (0-1) at the 6-month follow-up after surgery (Z = -4.248, P < .001). Postoperative complications included hyphema in 2 cases and vitreous hemorrhage in 1 case, and all 3 patients achieved satisfactory recovery with treatment. No drainage tube-related complications occurred among our patients. Long scleral tunnel technique is a safe and effective surgical treatment for NVG with fewer drainage tube-related complications.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Metabolite profiling of Drynariae Rhizoma using 1H NMR and HPLC coupled with multivariate statistical analysis.

Drynariae Rhizoma has been used to treat bone diseases and kidney deficiency in traditional medicine. Recently its aqueous extract was reported to enhance memory function. Although the Japanese standards for non-Pharmacopoeial crude drugs 2022 prescribed Drynaria roosii as the botanical origin, some counterfeits and both raw and stir-fired crude drugs are available in markets. To distinguish Drynariae Rhizoma derived from D. roosii appropriately from others and verify the validity of uses of stir-fried ones, 1H NMR-based metabolite profiling coupled with HPLC were performed. Raw samples derived from D. roosii contained naringin (1), neoeriocitrin (2), 5,7-dihydroxychromone-7-O-neohesperidoside (3), caffeic acid 4-O-ß-D-glucoside (4), protocatechuic acid (5), trans-p-coumaric acid 4-O-ß-D-glucoside (6), and kaempferol 3-O-α-L-rhamnoside 7-O-ß-D-glucoside (8). Stir-fried samples were characterized by presence of 5-hydroxymethyl-2-furaldehyde (13), and were divided into two types; one possessing similar composition to raw samples (Type I) and another without above components except 5 (Type II). Quantitative analyses using qHNMR and HPLC, followed by principal component analysis demonstrated that the raw samples had higher contents of 1 (0.93-9.86 mg/g), 2 (0.74-7.59 mg/g), 3 (0.05-2.48 mg/g), 4 (0.27-2.51 mg/g), 6 (0.14-1.26 mg/g), and 8 (0.04-0.52 mg/g), and Type II had a higher content of 5 (0.84-1.32 mg/g). The counterfeit samples derived from Araiostegia divaricata var. formosana were characterized by higher content of ( -)-epicatechin 3-O-ß-D-allopyranoside (10) (1.44-11.49 mg/g) without 1 and 2. These results suggested that Drynariae Rhizoma samples derived from other botanical origins and Type II stir-fried samples cannot substitute for D. roosii rhizome.