Objective To investigate the utility of dual-energy computed tomography(DECT)virtual non-contrast(VNC)images instead of true non-contrast(TNC)images in the quantitative analysis of emphysema.Methods A retrospective selection was con-ducted on 59 patients who underwent chest CT plain scan plus dual-phase enhanced scan on APEX-CT.VNC images of arterial phase(VNCart)and venous phase(VNCven)were generated on AW4.7 workstation.Volume CT dose index(CTDIvol)and dose length product(DLP)were recorded respectively.In a double-blind manner,two physicians graded the severity of each patient's emphysema according to the Fleischner Society's emphysema visual classification system.The"digital lung"detection and analysis platform was used to quantitatively measure emphysema at three thresholds(-950 HU,-930 HU and-910 HU),and the difference in meas-urement results between VNC images and TNC images was compared.Quantitative differences in low attenuation volume(LAV),percentage of low attenuation area(LAA%)and mean lung density(MLD)at the-950 HU threshold were compared using Bland-Altman plots.Results Using TNC images as the standard,there was no significant difference in the results of the visual classifica-tion evaluation of emphysema between TNC and VNC images(χ2=2.80,P=0.247).In quantitative measurement,there was no significant difference in total lung volume(TLV)(χ2=3.26,P=0.196)between the three groups images.Compared to TNC ima-ges,there were no statistically significant differences in LAV,LAA%and MLD of VNCven images at 15th percentile lung density(Perc 15%)and different thresholds(P>0.05).Compared to the TNC mode,the VNC mode could reduce the effective dose(ED)by approximately 32.6%.Conclusion The use of DECT VNCven images on chest has the potential to replace TNC for the quantitative analysis of emphysema,thereby streamlining scans and reducing radiation dose.

Objective To explore the clinical effect of totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunos-tomy for gastric cancer.Methods Ninety cases of gastric cancer patients were seleted,of which 45 cases undergoing Roux-en-Y esophagoje-junostomy for digestive tract reconstruction were set as the control group,while 45 cases undergoing hand-sewn esophagojejunostomy for digestive tract reconstruction were set as the observation group.Patients in the control group underwent laparoscopic-assisted total gastrectomy combined with Roux-en-Y esophagojejunostomy to reconstruct digestive tract,while patients in the observation group underwent totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunostomy to reconstruct digestive tract.The perioperative indicators and complications of patients in the two groups were compared.Results The surgical time,time of esophagojejunostomy,and time to get out of bed after surgery of patients in the observation group were significantly shorter than those in the control group(P<0.05),the pain score 24 hours after surgery was significantly lower than that in the control group(P<0.05).There was no statistically significant difference between the two groups in terms of the incidence of complications or Clavien-Dindo grading(P>0.05).Conclusion Hand-sewn esophagojejunostomy for digestive tract reconstruction has a good clinical effect in gastric cancer during totally laparoscopic total gastrectomy.It can shorten the surgical time and time of esophagojejunostomy,reduce postoperative pain,and accelerate postoperative recovery,whose safety is comparable to Roux-en-Y esophagojejunostomy.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective:To compare the clinical effects of different patches in laparoscopic inguinal hernia repair surgery for young male patients with inguinal hernia.Method:This study used a retrospective study design,117 young male patients with inguinal hernia who were admitted to our hospital from April 2022 to April 2024 were selected,all patients underwent laparoscopic inguinal hernia repair surgery,they were divided into Group A(41 cases,used polypropylene patches),Group B(37 cases,used self fixing patches)and Group C(39 cases,used 3D Max patches)according to the type of patch.Surgical indicators,visual analogue scale(VAS)scores at different time points,inflammatory stress indicators levels before and 1d after surgery[high sensitivity c-reactive protein(hs-CRP),cortisol(Cor),β-endorphine(β-EP),tumor necrosis factor-α(TNF-α)]and the incidence of postoperative complications and recurrence rate were compared among three groups.Result:The operation time and hospitalization time of Group B and Group C were shorter than those of Group A,and the intraoperative blood loss was less than that of Group A(P＜0.05).Compared with 1 d after surgery,VAS scores of the three groups at 3 d after surgery,7 d after surgery gradually decreased,VAS scores of the Group B at 3 d after surgery,7 d after surgery were lower than those in the Group A,VAS scores of the Group C at 3 d after surgery,7 d after surgery were lower than those in the Group B(P＜0.05).Compared with before surgery,hs-CRP,TNF-α,Cor and[3-EP increased among three groups at 1 d after suegrey,hs-CRP,TNF-α,Cor and β-EP of Group B at 1 d after surgery were lower than those of Group A(P＜0.05).hs-CRP,TNF-α,Cor and[3-EP of Group C at 1 d after surgery were lower than those of Group B(P＜0.05).The total incidence of postoperative complications and recurrence rate of Group B and Group C were lower than those of Group A(P＜0.05),and there was no significant difference in the total incidence of postoperative complications and recurrence rate between Group B and Group C(P＞0.05).Conclusion:Compared with polypropylene patches,3D Max patches and self fixing patches can better shorten surgical time and hospitalization time,reduce intraoperative blood,but 3D Max patches are more effective in reducing pain and inflammatory stress response.

Objective To investigate the utility of dual-energy computed tomography(DECT)virtual non-contrast(VNC)images instead of true non-contrast(TNC)images in the quantitative analysis of emphysema.Methods A retrospective selection was con-ducted on 59 patients who underwent chest CT plain scan plus dual-phase enhanced scan on APEX-CT.VNC images of arterial phase(VNCart)and venous phase(VNCven)were generated on AW4.7 workstation.Volume CT dose index(CTDIvol)and dose length product(DLP)were recorded respectively.In a double-blind manner,two physicians graded the severity of each patient's emphysema according to the Fleischner Society's emphysema visual classification system.The"digital lung"detection and analysis platform was used to quantitatively measure emphysema at three thresholds(-950 HU,-930 HU and-910 HU),and the difference in meas-urement results between VNC images and TNC images was compared.Quantitative differences in low attenuation volume(LAV),percentage of low attenuation area(LAA%)and mean lung density(MLD)at the-950 HU threshold were compared using Bland-Altman plots.Results Using TNC images as the standard,there was no significant difference in the results of the visual classifica-tion evaluation of emphysema between TNC and VNC images(χ2=2.80,P=0.247).In quantitative measurement,there was no significant difference in total lung volume(TLV)(χ2=3.26,P=0.196)between the three groups images.Compared to TNC ima-ges,there were no statistically significant differences in LAV,LAA%and MLD of VNCven images at 15th percentile lung density(Perc 15%)and different thresholds(P>0.05).Compared to the TNC mode,the VNC mode could reduce the effective dose(ED)by approximately 32.6%.Conclusion The use of DECT VNCven images on chest has the potential to replace TNC for the quantitative analysis of emphysema,thereby streamlining scans and reducing radiation dose.

Objective To explore the clinical effect of totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunos-tomy for gastric cancer.Methods Ninety cases of gastric cancer patients were seleted,of which 45 cases undergoing Roux-en-Y esophagoje-junostomy for digestive tract reconstruction were set as the control group,while 45 cases undergoing hand-sewn esophagojejunostomy for digestive tract reconstruction were set as the observation group.Patients in the control group underwent laparoscopic-assisted total gastrectomy combined with Roux-en-Y esophagojejunostomy to reconstruct digestive tract,while patients in the observation group underwent totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunostomy to reconstruct digestive tract.The perioperative indicators and complications of patients in the two groups were compared.Results The surgical time,time of esophagojejunostomy,and time to get out of bed after surgery of patients in the observation group were significantly shorter than those in the control group(P<0.05),the pain score 24 hours after surgery was significantly lower than that in the control group(P<0.05).There was no statistically significant difference between the two groups in terms of the incidence of complications or Clavien-Dindo grading(P>0.05).Conclusion Hand-sewn esophagojejunostomy for digestive tract reconstruction has a good clinical effect in gastric cancer during totally laparoscopic total gastrectomy.It can shorten the surgical time and time of esophagojejunostomy,reduce postoperative pain,and accelerate postoperative recovery,whose safety is comparable to Roux-en-Y esophagojejunostomy.