Objective To implement the disease prevention and control strategy of being ^"proactive and grassroots-focused,^" and to enhance the overall effectiveness of general hospitals in the tertiary prevention of cervical cancer, this consensus aims to provide an actionable guiding framework for the standardized construction of ^"Integrated Outpatient Clinics for Cervical Cancer Prevention and Control^" in general hospitals at all levels. Methods This consensus systematically elaborates on the specific elements for establishing such integrated clinics and formulates the corresponding standards. Results It is anticipated that the consensus will promote the establishment of standardized, homogeneous, and high-efficiency frontline positions for cervical cancer prevention and control within general hospitals, thereby contributing to the strategic vision of accelerating the elimination of cervical cancer. Conclusion The formulation and promotion of the consensus aim to provide robust clinical practice support for accelerating the realization of China's strategic vision of eliminating cervical cancer.

OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective: To evaluate the clinical value of a restrictive red blood cell transfusion strategy in orthopedic patients by retrospectively analyzing the current transfusion practices and comparing postoperative outcomes across different transfusion thresholds. Methods: Clinical data of patients who underwent orthopedic surgery and received blood transfusions at a single hospital from 2015 to 2020 were retrospectively collected for descriptive analysis. Patients were then stratified into two groups based on pre-transfusion hemoglobin (Hb) thresholds:70-79 g/L group (n=92) and 80-89 g/L group (n=120), and their data were compared in terms of postoperative hematological parameters, functional recovery, transfusion volume, and adverse events. Results: Among patients receiving orthopedic surgery and transfusion, elderly females accounted for a relatively high proportion. Transfusion requirements varied significantly across different surgical types, with marked differences in red blood cell transfusion volumes (P<0.001). Revision arthroplasty and spinal surgery had higher median volumes (3.5-3.0 U). Subgroup analysis revealed that the 70-79 g/L group had significantly higher postoperative D-dimer and creatinine levels than the 80-89 g/L group (Z=-2.035, P=0.042; Z=-2.523, P=0.012). The pre-transfusion pain score was also significantly higher in the 70-79 g/L group (Z=-2.828, P=0.005), but no significant difference was observed in post-transfusion pain scores between the two groups (P>0.05). Conclusion: This study did not observe significant differences in postoperative adverse events, functional recovery, or transfusion volume-related indicators between the two transfusion thresholds. These findings provide clinical reference data for future studies on the safety and applicability of restrictive transfusion strategies in the orthopedic perioperative setting.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (acupuncture for unblocking the obstruction in the governor vessel and regulating the spirit) on the depression-like behavior and the hippocampal neuronal ferroptosis mediated by solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway in depression rats, and explore the mechanism of this therapy for depression. METHODS: Of 30 male SD rats of SPF grade, 24 rats were selected. According to the random number table, they were divided into a normal group (n=8) and a modeling group (n=16). The rats in the modeling group were subjected to chronic unpredictable mild stress (CUMS) for 28 consecutive days to establish depression model. After modeling, 16 successfully-modeled rats were randomly divided into a model group and an acupuncture group, 8 rats in each one. In the acupuncture group, Tongdu Tiaoshen acupuncture was applied to "Dazhui"(GV14), "Shuigou" (GV26), "Baihui" (GV20) and "Shenting" (GV24). This intervention measure was deliveredonce a day, continuously for 6 days. The intervention discontinued on day 7, and was completed in 4 weeks. Before and after modeling, and after intervention completion, the behavioristics detection was performed using sucrose preference experiment and open field experiment. After intervention, using hematoxylin-eosin (HE) and Nissl staining, the morphology of hippocampal neurons was observed; with Western blot method, the protein expression of GPX4, SLC7A11, Ferritin and acyl-CoA synthetase long-chain family 4 (ACSL4) in hippocampal tissues was detected; with the real-time fluorescence quantitative PCR adopted, the mRNA expression of GPX4, SLC7A11, Ferritin and ACSL4 was detected; and using colorimetry, the hippocampal iron content was determined. RESULTS: After modeling, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the model group and the acupuncture group were lower than those in the normal group (P<0.01). After the intervention, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the acupuncture group were higher than those in the model group (P<0.01, P<0.05). Compared with the normal group, the number of necrotic cells increased and the number of Nissl bodies decreased in the model group; and when compared with the model group, the neuronal pyknosis and necrosis were ameliorated, the cells were arranged more regularly, the neuronal structure was clear, the matrix was dense, the blood vessels were enriched and the number of Nissl bodies increased in the acupuncture group. In comparison with the normal group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 decreased (P<0.01), it increased in the expression of hippocampal Ferritin and ACSL4 (P<0.01) in the model group. When compared with the model group, in the acupuncture group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 was elevated (P<0.01, P<0.05), it was dropped for hippocampal Ferritin and ACSL4 (P<0.01). In the model group, the hippocampal iron content was elevated when compared with that in the normal group (P<0.01); and it was reduced in the acupuncture group when compared with that in the model group (P<0.05). CONCLUSION Tongdu Tiaoshen acupuncture attenuates depression-like behaviors in the depression rats, which may be related to regulating SLC7A11/GPX4 pathway and inhibiting neuronal ferroptosis in the hippocampus.
Animals ; Ferroptosis ; Male ; Hippocampus/cytology* ; Rats, Sprague-Dawley ; Rats ; Depression/enzymology* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Acupuncture Therapy ; Neurons/metabolism* ; Humans ; Acupuncture Points ; Amino Acid Transport System y+/genetics* ; Glutathione Peroxidase/genetics*