Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

ObjectiveTo explore the potential mechanism of Weicanqing Formula （微残清方， WF） combined with chemotherapy in treating acute myeloid leukemia （AML） based on malic enzyme 2 （ME2）-mediated bone marrow immune-metabolic homeostasis and . MethodsSixty-five male C57BL/6N mice were randomly divided into control group， model group， WF group， chemotherapy group， and the combination group （WF plus chemotherapy）， with 13 mice per group. Except for the control group， mice were injected with C1498 cells （appro-ximately 1×10⁶ cells per mouse） via the tail vein on day 1 to establish an AML model. Starting from day 8， mice in the chemotherapy group and the combination group were administered with cytarabine at 30 mg/（kg·d） via subcutaneous injection， once daily for 3 consecutive days； WF group and the combination group received WF at 7.54 g/（kg·d） by gavage， once daily for 21 consecutive days. On days 1， 7， 14， 21 and 28， hemoglobin （Hb） and white blood cell （WBC） levels were determined in each group. On day 28， Giemsa staining was used to observe morphological changes in bone marrow cells. Flow cytometry was employed to detect the expression levels of bone marrow T lympthocyte subsets， including CD8⁺， CD4⁺， and regulatory T lymphocytes （Treg）. The contents of glutamine （Gln）， nicotinamide adenine dinucleotide phosphate （NADP⁺）， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in bone marrow were determined using visible spectrophotometry. Adenosine triphosphate （ATP） concentration in bone marrow was measured by chemiluminescence assay. The mRNA expression of malic enzyme 2 （ME2） in bone marrow was detected by RT-qPCR， and the protein expression level of ME2 was determined by Western blotting. ResultsCompared to the control group， the model group showed decreased Hb levels on day 14， 21， and 28， and increased WBC levels on day 7， 14， 21， and 28 （P＜0.05）. On day 28， bone marrow CD8⁺ and CD8⁺/CD4⁺ levels decreased， while Treg cells， ATP， Gln， NADP⁺， NADPH， ME2 mRNA， and their corresponding protein levels increased （P＜0.05）. Compared to the model group， the chemotherapy group and the combination group both exhibited reduced Hb level on day 14， 21 and 28， as well as the increased WBC level； the combination group showed increased CD8⁺ level， decreased Treg， ATP， Gln， and NADPH content， as well as reduced ME2 mRNA expression and protein levels （P＜0.05）. Compared to the chemotherapy group， the combination group showed significantly increased Hb level on days 21 and 28， and increased WBC level on day 28 （P＜0.05）. Bone marrow smear pathology revealed that， in the model group， myeloid blast cells exhibited cytoplasmic vacuoles indicative of abnormal metabolic activity. In contrast， both the chemotherapy group and the combination group showed large numbers of metamyelocytes and band neutrophils， with only a few immature granulocytic blast cells observed. ConclusionWF may improve the prognosis of AML when used as an adjunct to chemotherapy by modulating ME2 expression， inhibiting metabolic energy competition within the bone marrow microenvironment， and reshaping the distribution of T lymphocyte subsets in the bone marrow.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Objective:To investigate the changes in accommodative facility after implantation of V4c implantable collamer lens (ICL) using the intelligent flipper (iFLIP).Methods:A serial case-control study was conducted.Forty patients (80 eyes) who underwent ICL implantation of V4c for myopia correction and completed the follow-up were enrolled at the Affiliated Hospital of Guizhou Medical University from April 2022 to April 2023.Monocular and binocular accommodative facility, adjustment time, and relaxation time were measured with iFLIP before operation and at 1 week, 1 month, 3 months, and 6 months after operation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (No.2023-983).Written informed consent was obtained from each subject.Results:Monocular and binocular uncorrected visual acuity at 1 week, 1 month, 3 months and 6 months after surgery were significantly improved compared with before surgery, and the differences were statistically significant (all P<0.05).Monocular and binocular postoperative accommodative facility gradually increased over time, and the increase gradually decreased and gradually stabilized.Before operation and 1 week, 1 month, 3 months, and 6 months after operation, the monocular accommodative facility was (7.99±3.42), (10.19±4.25), (12.03±4.24), (13.10±4.66) and (13.64±4.40)cpm, and the binocular accommodative facility was (9.01±3.63), (9.56±3.38), (11.58±4.00), (13.31±3.64), and (14.03±3.72)cpm, respectively, with statistically significant overall differences ( F=24.02, 14.46; both P<0.001).Monocular accommodative facility was higher than before surgery at each time point after surgery, and was higher than 1 week after surgery at 1, 3, and 6 months after surgery, with statistically significant differences (all P<0.05).Binocular accommodative facility was higher at 1, 3, and 6 months after surgery than that before surgery and 1 week after surgery, and higher at 3 and 6 months after surgery than that at 1 month after surgery, with statistically significant differences (all P<0.05).With the extension of postoperative time, the monocular and binocular adjustment time and relaxation time gradually shortened, and the shortening gradually decreased and stabilized.Monocular adjustment time and relaxation time were shorter than before surgery at all time points after surgery.The monocular adjustment time was shorter at 1, 3 and 6 months after surgery than that at 1 week after surgery and shorter at 3 and 6 months after surgery than that at 1 month after surgery, and the monocular relaxation time was shorter at 3 and 6 months after surgery than that at 1 week after surgery, and the differences were statistically significant (all P<0.05).The binocular adjustment time was shorter at 1, 3 and 6 months after surgery than before surgery and at 1 week after surgery, shorter at 3 and 6 months after surgery than at 1 month after surgery and the binocular relaxation time was shorter at all time points after surgery than that before surgery, showing statistically significant differences (all P<0.05). Conclusions:After ICL implantation, uncorrected visual acuity, accommodative facility, adjustment time and relaxation time all improve throughout the preoperative period and eventually stabilize.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Objective:To explore the direct effect of safety organization on work engagement of Operating Room nurses, as well as the mediating effect of psychological capital between safety organization and work engagement, so as to provide theoretical basis for developing intervention programs to enhance work engagement of Operating Room nurses.Methods:From October to December 2024, convenience sampling was used to select 260 Operating Room nurses from three ClassⅢ Grade A hospitals as research subjects. Psychological Capital Questionnaire, Safety Organizing Scale, and Work Engagement Scale were used to survey Operating Room nurses. AMOS 26.0 software was used to analyze the mediating effect of Operating Room nurses' psychological capital between safety organization and work engagement.Results:A total of 260 questionnaires were distributed and 241 valid questionnaires were recovered, with a valid recovery rate of 92.69%. Among 241 Operating Room nurses, the total scores of Work Engagement Scale, Psychological Capital Questionnaire, and Safety Organizing Scale were (37.35±7.30), (90.10±11.62), and (41.58±10.82), respectively. The total score and scores of each dimension of the Work Engagement Scale were positively correlated with the total score and scores of each dimension of the Psychological Capital Questionnaire and the total score of the Safe Organizing Scale ( P<0.05). The total score and scores of each dimension of the Psychological Capital Questionnaire were positively correlated with the total score of the Safe Organizing Scale ( P<0.05). Mediating effect analysis showed that the direct effect of safety organization on work engagement of Operating Room nurses was established, with an effect value of 0.266 ( P<0.05). Psychological capital played a partially mediating effect between safety organization and work engagement of, with an effect value of 0.275, and the mediating effect accounted for 50.83% of the total effect. Conclusions:Safety organization has a positive impact on work engagement of Operating Room nurses, and psychological capital partially mediates the effect between safety organization and work engagement of Operating Room nurses. Hospital nursing administrators should be aware of the importance of building a safety organization and pay attention to building the psychological capital of Operating Room nurses so as to improve work engagement.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.