A functional variant rs10409772 in FUT6 promoter regulates colorectal cancer progression through PKA/CREB signaling.

Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation. Moreover, FUT6 expression is regulated by rs10409772 shown in the luciferase essays, a single nucleotide polymorphism in the promoter of FUT6. Our study suggests that elevated expression of FUT6 promotes PKA/CREB signaling, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased FUT6 expression.

Automatic grading evaluation of winter wheat lodging based on deep learning.

Lodging is a crucial factor that limits wheat yield and quality in wheat breeding. Therefore, accurate and timely determination of winter wheat lodging grading is of great practical importance for agricultural insurance companies to assess agricultural losses and good seed selection. However, using artificial fields to investigate the inclination angle and lodging area of winter wheat lodging in actual production is time-consuming, laborious, subjective, and unreliable in measuring results. This study addresses these issues by designing a classification-semantic segmentation multitasking neural network model MLP_U-Net, which can accurately estimate the inclination angle and lodging area of winter wheat lodging. This model can also comprehensively, qualitatively, and quantitatively evaluate the grading of winter wheat lodging. The model is based on U-Net architecture and improves the shift MLP module structure to achieve network refinement and segmentation for complex tasks. The model utilizes a common encoder to enhance its robustness, improve classification accuracy, and strengthen the segmentation network, considering the correlation between lodging degree and lodging area parameters. This study used 82 winter wheat varieties sourced from the regional experiment of national winter wheat in the Huang-Huai-Hai southern area of the water land group at the Henan Modern Agriculture Research and Development Base. The base is located in Xinxiang City, Henan Province. Winter wheat lodging images were collected using the unmanned aerial vehicle (UAV) remote sensing platform. Based on these images, winter wheat lodging datasets were created using different time sequences and different UAV flight heights. These datasets aid in segmenting and classifying winter wheat lodging degrees and areas. The results show that MLP_U-Net has demonstrated superior detection performance in a small sample dataset. The accuracies of winter wheat lodging degree and lodging area grading were 96.1% and 92.2%, respectively, when the UAV flight height was 30 m. For a UAV flight height of 50 m, the accuracies of winter wheat lodging degree and lodging area grading were 84.1% and 84.7%, respectively. These findings indicate that MLP_U-Net is highly robust and efficient in accurately completing the winter wheat lodging-grading task. This valuable insight provides technical references for UAV remote sensing of winter wheat disaster severity and the assessment of losses.

Needle-perc-assisted endoscopic surgery versus retrograde intrarenal surgery for the treatment of 1- to 2-cm lower-pole renal stones in patients with unfavorable infundibulopelvic anatomy: a matched-pair analysis.

PURPOSE: To compare the safety and efficacy of needle-perc-assisted endoscopic surgery (NAES) and retrograde intrarenal surgery (RIRS) for the treatment of 1- to 2-cm lower-pole stones (LPS) in patients with complex infundibulopelvic anatomy. METHODS: Between June 2020 and July 2022, 32 patients with 1- to 2-cm LPS and unfavorable lower-pole anatomy for flexible ureteroscopy were treated with NAES. The outcomes of these patients were compared with patients who underwent RIRS using matched-pair analysis (1:1 scenario). The matching parameters such as age, gender, body mass index, stone size, hardness, and pelvicalyceal anatomy characteristics including infundibular pelvic angle, infundibular length, and width were recorded. Data were analyzed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test. RESULTS: The two groups had similar baseline characteristics and lower-pole anatomy. The stone burden was comparable between both groups. NASE achieved a significantly better initial stone-free rate (SFR) than RIRS (87.5% vs 62.5%, p = 0.04). The auxiliary rates for the NAES and RIRS groups were 12.5% and 31.3%, respectively (p = 0.13). Finally, the SFR after 1 month follow-up period was still higher for the NAES group than RIRS group (93.8% versus 81.3%), but the difference was not statistically significant (p = 0.26). Concerning the operation duration, overall complication rates, and postoperative hospital stay, there were no differences between two groups. CONCLUSION: Compared to RIRS for treating 1- to 2-cm LPS in patients with unfavorable infundibulopelvic anatomy for flexible ureteroscopy, NAES was safe and effective with higher SFR and similar complication rate.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.

Dynamic video recognition for cell-encapsulating microfluidic droplets.

Droplet microfluidics is a highly sensitive and high-throughput technology extensively utilized in biomedical applications, such as single-cell sequencing and cell screening. However, its performance is highly influenced by the droplet size and single-cell encapsulation rate (following random distribution), thereby creating an urgent need for quality control. Machine learning has the potential to revolutionize droplet microfluidics, but it requires tedious pixel-level annotation for network training. This paper investigates the application software of the weakly supervised cell-counting network (WSCApp) for video recognition of microdroplets. We demonstrated its real-time performance in video processing of microfluidic droplets and further identified the locations of droplets and encapsulated cells. We verified our methods on droplets encapsulating six types of cells/beads, which were collected from various microfluidic structures. Quantitative experimental results showed that our approach can not only accurately distinguish droplet encapsulations (micro-F1 score > 0.94), but also locate each cell without any supervised location information. Furthermore, fine-tuning transfer learning on the pre-trained model also significantly reduced (>80%) annotation. This software provides a user-friendly and assistive annotation platform for the quantitative assessment of cell-encapsulating microfluidic droplets.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

AIMS: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Cadaveric study of flexor digitorum profundus and superficialis and flexor pollicis longus innervation patterns for application in selective neurectomy.

PURPOSE: Spasticity management in finger flexors (flexor digitorum profundus and superficialis and flexor pollicis longus) is a challenge. Recent studies demonstrated the short- and long-term efficacy of selective and hyperselective neurectomy for the spastic upper limb. However, hyperselective neurectomy of flexor digitorum profundus and flexor digitorum superficialis branches was incomplete, without impairing their muscular body and function. This cadaveric study describes a novel medial approach in the forearm, to reach all the muscular branches: flexor digitorum superficialis and profundus and flexor pollicis longus. MATERIAL AND METHODS: Fourteen cadaveric fresh frozen upper limbs were used. The feasibility of the medial surgical approach was studied, as well as the number, length and point of emergence of the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis. RESULTS: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, in all cases. A Martin Gruber communicating branch was found in 7 cases out of 14. CONCLUSION: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerve to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, without extensive transmuscular dissection of the pronator teres or flexor digitorum superficialis muscles. This approach opens the way for selective neurectomy of the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis muscles. LEVEL OF EVIDENCE: IV.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

Transcription factor 12-mediated self-feedback regulatory mechanism is required in DUX4 fusion leukaemia.

BACKGROUND: IGH::DUX4 is frequently observed in 4% B-cell acute lymphoblastic leukaemia patients. Regarding the IGH::DUX4-driven transactivation and alternative splicing, which are the main reasons behind this acute leukaemia outbreak, it remains unclear how transcriptional cofactors contribute to this oncogenic process. Further investigation is required to elucidate their specific role in leukaemogenesis. METHODS: In order to investigate the cofactors of IGH::DUX4, integrated mining of Chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing of leukaemia cells and patient samples were conducted. Furthermore, to elucidate the synergistic interaction between transcription factor 12 (TCF12) and IGH::DUX4, knockdown and knockout experiment, mammalian two-hybridisation assay, co-immunoprecipitation and in situ proximity ligation assays were carried out. Additionally, to further investigate the direct interaction between TCF12 and IGH::DUX4, AI-based structural simulations were utilised. Finally, to validate the synergistic role of TCF12 in promoting IGH::DUX4 leukaemia, cell proliferation, apoptosis and drug sensitivity experiments were performed. RESULTS: In this study, we observed that the IGH::DUX4 target gene TCF12 might be an important cofactor/helper for this oncogenic driver. The co-expression of IGH::DUX4 and TCF12 resulted in enhanced DUX4-driven transactivation. Supportively, knockdown and knockout of TCF12 significantly reduced expression of IGH::DUX4-driven target genes in leukaemia REH (a precursor B-cell leukaemia cell line) and NALM-6 cells (a precursor B-cell leukaemia cell line). Consistently, in TCF12 knockout cells, the expression of structure-based TCF12 mutant, but not wild-type TCF12, failed to restore the TCF12-IGH::DUX4 crosstalk and the synergistic transactivation. More importantly, the breakdown in TCF12-IGH::DUX4 cooperation impaired IGH::DUX4-driven leukaemia cell survival, caused sensitivity to the chemotherapy. CONCLUSIONS: Altogether, these results helped to define a previously unrecognised TCF12-mediated positive self-feedback regulatory mechanism in IGH::DUX4 leukaemia, which holds the potential to function as a pivotal drug target for the management of this particular form of leukaemia. HIGHLIGHTS: Transcription factor 12 (TCF12) is a new novel cofactor in IGH::DUX4 transcriptional complexes/machinery. TCF12 mediates a positive self-feedback regulatory mechanism in IGH::DUX4-driven oncogenic transaction. IGH::DUX4-TCF12 structure/cooperation might represent a potent target/direction in future drug design against B-cell acute lymphoblastic leukaemia.

Transfer of the palmaris brevis motor branch to the thenar motor branch: A cadaveric preliminary study.

OBJECTIVE: High median nerve injuries can lead to poor distal recovery, especially poor functioning of median innervated thenar muscles involved in thumb opposition and palmar abduction. The palmaris brevis (PB) is a small subcutaneous muscle innervated by ulnar nerve. Innervation of the PB is in most of cases provided by the ulnar digital nerve to the little finger. The purpose of this study is to assess the feasibility of transferring the PB motor branch (PBMB) to the median nerve thenar motor branch (TMB), in order to allow for early restoration of thumb palmar abduction and opposition, through a preliminary cadaveric study. METHODS: Twenty-five cadaver upper limbs were dissected under magnification. The length of the PBMB and TMB, and their origin were recorded. Nerve transfer from PBMB to TMB was conducted, and evaluated on 2 parameters: surgical feasibility, and distance from the coaptation site to the recipient nerve muscle entry point. The PBMB and TMB were harvested, fixated in formalin, then embedded in paraffin. They were sectioned transversely, and stained with a combination of hematoxylin-eosin and Luxol fast blue. Myelinated axons were counted in each specimen and the donor-to-recipient axon ratio was recorded. RESULTS: The PBMB was constant and originated from the ulnar digital nerve of the little finger in all cases. The transfer from PBMB to TMB was feasible in all cases. Mean myelinated axon counts of PBMB and TMB were 253±142 and 356±198, respectively (p=0.06). The donor-to-recipient axon ratio was 1:1.41. The mean distance from coaptation of the PBMB to the recipient thenar muscles was 23.1±3.0mm. CONCLUSIONS: Based on our results, PBMB to TMB transfer is feasible. The PBMB has the advantage over other distal nerve transfer donors to be constant and superficial, allowing for an easier harvest. Moreover, this procedure does not sacrifice any intrinsic function of the hand, and the proximity of the PBMB with the carpal tunnel allows for a single incision procedure. Therefore, early restoration of the median innervated thenar muscles may be feasible by the PBMB to TMB transfer in cases of high median nerve lesions. LEVEL OF EVIDENCE: IV.

Needle-perc-assisted endoscopic surgery (NAES) for patients with complicated solitary kidney stones: a prospective randomized study from a single center.

PURPOSE: The goal of this study is to compare traditional percutaneous nephrolithotomy (PCNL) and needle-perc-assisted endoscopic surgery (NAES) in the treatment of complicated solitary kidney stones via a single-center randomized controlled prospective study. METHODS: A total of patients with complex (Guy's score II-IV) solitary kidney stones between July 2019 to June 2022 were enrolled in the study. Participants were stratified into two groups: needle-perc-assisted endoscopic surgery group (group A) and traditional PCNL group (group B). All procedures were finished by X-ray free technique. The clinical characteristics and outcomes were analyzed. RESULTS: A total of 90 (44 in Group A and 46 in Group B) patients were finally included in our study. There were no statistically differences in terms of gender, age, body mass index (BMI), stone burden between two groups. The mean operative duration of Group A was significant higher than group B (95.1 ± 21.4 min vs 72.5 ± 29.5 min, p=0.02). The 1-month stone-free rate (SFR) was significant higher in Group A than B (90.9% vs 73.9%, p=0.03). A less hemoglobin drop (p=0.01), shorter postoperative in-hospital day (p=0.04), and lower severe complication (Clavien-Dindo III and above) rates (p=0.03) were observed in Group A. CONCLUSION: For patients with solitary kidney stones, NAES technique provides a higher one-session SFR, a better renal function recovery and compared with traditional PCNL.

Jackstone in the renal calyx: A rare case report.

BACKGROUND: Jackstone is a rare entity of calculi in urinary tracts and has the characteristic appearance resembling toy jacks. They are nearly always reported to occur in the urinary bladder, we first report a rare case of jackstone located in the obstructed renal calyx. CASE SUMMARY: We report a 46-year-old man presenting with intermittent, painless gross hematuria and left flank pain. Urinary computed tomography revealed staghorn stones and secondary hydronephrosis. A jackstone with radiating branches was found in one of the dilated renal calyx. Percutaneous nephrolithotomy was performed and endoscopic images were recorded during the operation. Postoperative stone composition analysis revealed it as calcium oxalate monohydrate stones. CONCLUSION: Jackstones can occur in the renal collecting system besides the bladder. The unique appearance and imaging manifestations are the most important factors in the diagnosis of jackstones, and further exploration of the formation mechanism is required.

Feedback regulation of ubiquitination and phase separation of HECT E3 ligases.

Lipid homeostasis is essential for normal cellular functions and dysregulation of lipid metabolism is highly correlated with human diseases including neurodegenerative diseases. In the ubiquitin-dependent autophagic degradation pathway, Troyer syndrome-related protein Spartin activates and recruits HECT-type E3 Itch to lipid droplets (LDs) to regulate their turnover. In this study, we find that Spartin promotes the formation of Itch condensates independent of LDs. Spartin activates Itch through its multiple PPAY-motif platform generated by self-oligomerization, which targets the WW12 domains of Itch and releases the autoinhibition of the ligase. Spartin-induced activation and subsequent autoubiquitination of Itch lead to liquid-liquid phase separation (LLPS) of the poly-, but not oligo-, ubiquitinated Itch together with Spartin and E2 both in vitro and in living cells. LLPS-mediated condensation of the reaction components further accelerates the generation of polyubiquitin chains, thus forming a positive feedback loop. Such Itch-Spartin condensates actively promote the autophagy-dependent turnover of LDs. Moreover, we show that the catalytic HECT domain of Itch is sufficient to interact and phase separate with poly-, but not oligo-ubiquitin chains. HECT domains from other HECT E3 ligases also exhibit LLPS-mediated the promotion of ligase activity. Therefore, LLPS and ubiquitination are mutually interdependent and LLPS promotes the ligase activity of the HECT family E3 ligases.

RNA modification-mediated translational control in immune cells.

RNA modifications play a vital role in multiple pathways of mRNA metabolism, and translational regulation is essential for immune cells to promptly respond to stimuli and adapt to the microenvironment. N6-methyladenosine (m6A) methylation, which is the most abundant mRNA modification in eukaryotes, primarily functions in the regulation of RNA splicing and degradation. However, the role of m6Amethylation in translational control and its underlying mechanism remain controversial. The role of m6A methylation in translation regulation in immune cells has received relatively limited attention. In this review, we aim to provide a comprehensive summary of current studies on the translational regulation of m6A modifications and recent advances in understanding the translational control regulated by RNA modifications during the immune response. Furthermore, we envision the possible pathways through which m6A modifications may be involved in the regulation of immune cell function via translational control.

ChatGPT Performs on the Chinese National Medical Licensing Examination.

ChatGPT, a language model developed by OpenAI, uses a 175 billion parameter Transformer architecture for natural language processing tasks. This study aimed to compare the knowledge and interpretation ability of ChatGPT with those of medical students in China by administering the Chinese National Medical Licensing Examination (NMLE) to both ChatGPT and medical students. We evaluated the performance of ChatGPT in three years' worth of the NMLE, which consists of four units. At the same time, the exam results were compared to those of medical students who had studied for five years at medical colleges. ChatGPT's performance was lower than that of the medical students, and ChatGPT's correct answer rate was related to the year in which the exam questions were released. ChatGPT's knowledge and interpretation ability for the NMLE were not yet comparable to those of medical students in China. It is probable that these abilities will improve through deep learning.

Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type.

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.

A Reversible Fluorescent Probe for In Situ Monitoring Redox Imbalance during Mitophagy.

Mitophagy is the lysosome-dependent degradation of damaged and dysfunctional mitochondria, which is closely associated with H2O2-related redox imbalance and pathological processes. However, development of fast-responding and highly sensitive reversible fluorescent probes for monitoring of mitochondrial H2O2 dynamics is still lacking. Herein, we report a reversible fluorescent probe (M-HP) that enables real-time imaging of H2O2-related redox imbalance. In vitro studies demonstrated that M-HP had a rapid response and high sensitivity to the H2O2/GSH redox cycle, with a detection limit of 17 nM for H2O2. M-HP was applied to imaging of H2O2 fluctuation in living cells with excellent reversibility and mitochondrial targeting. M-HP reveals an increase in mitochondrial H2O2 under lipopolysaccharide stimulation and a decrease in H2O2 following the combined treatment with rapamycin. This suggests that the level of oxidative stress is significantly suppressed after the enhancement of mitophagy. The rationally designed M-HP offers a powerful tool for understanding redox imbalance during mitophagy.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial.

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.