Objective To explore the effect of electroacupuncture at the Neiguan and Jianshi acupoints on the brain functional network connectivity in APP/PS1 mice. Methods A total of 18 5-month-old SPF-grade male mice were selected， among which 12 model mice carrying the APP/PS1 double transgenic were randomly divided into two groups according to the random number table method： the model group （n = 6） and the electroacupuncture group （n = 6）. Additionally， 6 C57BL/6 mice with the same genetic background were selected as the control group. The mice in the electroacupuncture group were given electroacupuncture intervention at the "Neiguan" and "Jianshi" acupoints. The electroacupuncture device was connected to the acupoints on the same side， and the acupoints on both sides were alternately used once every other day for a total of 5 weeks. After electroacupuncture， the spatial learning and memory ability of mice in each group was detected by Morris water maze， and the non-spatially dependent memory ability of mice in each group was observed by new object recognition. Taking the bilateral hippocampus as the region of interest （ROI）， resting-state functional magnetic resonance imaging （rs-fMRI） was used to analyze the functional connectivity between the hippocampus and the whole brain. The changes in the contents of norepinephrine （NE） and dopamine （DA） in the hippocampus and prefrontal cortex were detected by ELISA. The expression levels of glycogen synthase kinase 3β （GSK-3β） and synaptic protein I（SynI） in the hippocampus were detected by Western blot. Results Compared with the control group， the latency of mice in the model group was prolonged （P < 0.01）， the number of platform crossings and the exploration time of the target quadrant decreased （P < 0.01）， and the cognitive index decreased （P < 0.01）. Compared with the model group， the latency of mice in the electroacupuncture group was shortened （P < 0.01）， the number of platform crossings and the exploration time of the target quadrant were both increased （P < 0.01）， and the cognitive index was elevated （P < 0.01）. Compared with the control group， the functional connections of the transition area between the right hippocampus and the left posterior piriform region， the right central amygdala， the left dentate gyrus， the right entorhinal region， and the right main olfactory bulb in the model group mice were decreased. Compared with the model group， the functional connections of the transition area between the right hippocampus and the left posterior piriform region， the right central amygdala， the transition area of the right posterior piriform region， the left dentate gyrus， the right main olfactory bulb， and the left main olfactory bulb in the electroacupuncture group were increased. The functional connections between the left hippocampus and the right lateral nucleus， the right hippocampal subCA3， the left main olfactory bulb， and the left entorhinal area were elevated. Compared with the control group， the contents of NE and DA in the hippocampus of mice in the model group decreased （P < 0.05）， and the contents of NE and DA in the prefrontal cortex decreased （P < 0.05）. Compared with the model group， the contents of NE and DA in the hippocampus of mice in the electroacupuncture group increased （P < 0.05）， and those in the prefrontal cortex increased （P < 0.05）. Compared with the control group， the expression of GSK-3β in the hippocampus of mice in the model group increased and the expression of SynI decreased （P < 0.05）. Compared with the model group， the expression of GSK-3β in the hippocampus of mice in the electroacupuncture group decreased and the expression of SynI increased （P < 0.05）. Conclusions Electroacupuncture at the pericardium acupoint can restore the functional connectivity between the hippocampus and other brain regions in APP/PS1 mice. The mechanism may be related to the disorder of neurotransmitters regulating the key brain regions of AD.

Objective To observe the effect of human umbilical cord mesenchymal stem cells （HUC-MSCs） transplantation on aquaporin-4（AQP4）after white matter injury（WMI）in neonatal rats，and to evaluate the repair effect on blood-brain barrier and its possible mechanism. Methods A total of 90 2-day-old Sprague-Dawley（SD）rats were randomly divided into three groups：the sham operation group，the WMI group，and the HUC-MSCs group，with 30 rats in each group.The WMI model of neonatal rats was constructed by intraperitoneal injection of low dose lipopolysaccharide（0.05 mg/kg），unilateral common carotid artery ligation combined with hypoxia（8% oxygen + 92% nitrogen）.The HUC-MSCs group was transplanted with 2×10⁵ HUC-MSCs at a dose of 2 μL by a brain stereotaxic apparatus within 2 hours after modeling.Samples were collected and tested at different time points after modeling.The brain water content of rats in each group was detected by wet and dry weight measurement；The pathological changes of brain tissue in each group were observed by hematoxylin-eosin staining； Immunohistochemical staining was used to observe the expression sites and levels of glial fibrillary acidic protein （GFAP）， AQP4 and myelin basic protein （MBP） in brain tissues，the expression levels of AQP4，GFAP and MBP protein in each group were detected by Weston blot，the memory and spatial exploration ability of rats in each group were observed by Morris water maze test，and the concentration of Evans blue in each group was detected by Evans blue test. Results Compared with the sham operation group，the WMI group showed loose nerve fiber arrangement，disordered shape，nuclear pyknosis and nuclear lysis. The situation in the HUC-MSCs group was improved compared with the WMI group. Compared with the sham group， the brain water content in the WMI group increased （all P < 0.05）； Brain water content decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. Compared with the sham group， the content of Evans blue in the brain tissue of the WMI group and the HUC-MSCs group increased， and decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. The expression of MBP in the WMI group and HUC-MSCs group decreased compared with the sham group， which increased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. And the expression of GFAP in the WMI group and HUC-MSCs group increased compared with the sham group， and it decreased in the HUC-MSCs group compared with the WMI group （all P < 0.05）. AQP4 had the same trend as GFAP （all P < 0.05）. The escape incubation period of WMI group and HUC-MSCs group was prolonged， the number of platforms crossed and the time stayed in the target quadrant were shortened compared with the sham group； and the escape incubation period was shortened， the number of platforms crossed and the time spent in the target quadrant increased in the HUC-MSCs group compared with the WMI group（all P < 0.05）. Conclusion HUC-MSCs have a certain repair effect on WMI blood-brain barrier in neonatal rats， and the mechanism may be related to the inhibition of astrocyte activation and down-regulation AQP4 protein expression.

Objective To investigate whether psychological stress causes duodenal inflammation and the related molecular mechanisms. Methods This study employed a chronic restraint stress （CRS） mouse model， which was supplemented with in vitro models using RAW264.7 and THP-1 monocytic/macrophage cell lines. Techniques including RT-qPCR， Western blot， HE staining， and immunohistochemistry were used to investigate the expression alterations of inflammatory cytokines， pyroptosis pathway-related proteins， and hormone receptors. Results CRS significantly triggered an inflammatory response in the duodenal tissue of mice， which was characterized by heightened levels of inflammatory cytokines such as IL-1β， IL-18， and TNF-α， along with elevated histological scores （P < 0.05）. This pro-inflammatory effect was mediated by the β2-adrenergic receptor （β2AR）， rather than the glucocorticoid receptor. Further research demonstrated that CRS facilitated the proliferation of macrophages in the duodenal mucosa， and the chemical depletion of macrophages effectively inhibited CRS-induced inflammation （P < 0.01）. Mechanistically， CRS activated the classical NLRP3/Caspase1/GSDMD-mediated pyroptosis pathway in duodenal macrophages， as indicated by the increased protein level of the activated N-terminal fragment of GSDMD. In vitro experiments verified that the stress hormone epinephrine could directly activate the macrophage pyroptosis pathway and stimulate the release of inflammatory cytokines via β2AR （P < 0.05）. Conclusions Psychological stress triggers the activation of the sympathetic-adrenal medulla system. This activation promotes GSDMD-mediated pyroptosis in duodenal macrophages through the β2AR signaling pathway， ultimately resulting in duodenal mucosal inflammation.

Objective To explore the value and clinical significance of cone beam computed tomography （CBCT） in measuring alveolar bone changes in patients with periodontitis. Methods The clinical data of 126 patients with periodontitis （2，764 teeth） admitted to the First Affiliated Hospital of Anhui Medical University from January 2023 to January 2025 were retrospectively analyzed， and the above patients received periodental non-surgical treatment for 6 months. The differences in alveolar bone defect height （BDH） and alveolar bone mineral density （BMD） before and after treatment were compared among patients with different genders， different ages， different severities of periodontitis and different teeth positions. Results Before and after treatment， male patients exhibited higher BDH and BMD than female patients （P < 0.05）. After treatment， BDH of patients with different genders was decreased while BMD was increased compared to before treatment （P < 0.05）. Before and after treatment， BDH comparison of patients of different ages was the highest in patients over 50 years old， followed by patients with 30-50 years old and patients under 30 years old. BMD comparison was the lowest in patients over 50 years old， followed by patients with 30-50 years old， and was the highest in patients under 30 years old. After treatment， BDH in patients over 50 years old and 30-50 years old was lowered （P < 0.05） while BMD was elevated compared to before treatment （P < 0.05）. There were no statistical differences in BDH and BMD in patients under 30 years old compared to before treatment （P > 0.05）. Before and after treatment， the BDH of patients with different severities of periodontitis was manifested as severe patients>moderate patients>mild patients， while BMD was shown as severe patients<moderate patients<mild patients （P < 0.05）， mainly revealing mesial side>distal side>buccal side>lingual side. After treatment， BDH in mild， moderate and severe patients was reduced while BMD was enhanced compared to before treatment （P < 0.05）. Comparison of BDH in different positions before and after treatment revealed molar area>premolar area>anterior teeth area， and BMD comparison showed molar area<premolar area<anterior teeth area （P < 0.05）， and mesial side> distal side>buccolingual side. After treatment， BDH in molar area and premolar area was lower than that before treatment while BMD was higher than that before treatment （P < 0.05）. There were no statistical differences in BDH and BMD in the anterior teeth area before and after treatment （P > 0.05）. Conclusion CBCT images can effectively quantify the changes of alveolar bone in periodontitis， and can provide a scientific basis for the accurate diagnosis and treatment of periodontitis by imaging methods.

Objective To investigate the prognostic value of combined assessment of the pulmonary artery pulsatility index （PAPi） and the myocardial microcirculation index in elderly patients with chronic heart failure with reduced ejection fraction （HFrEF）. Methods From January 2024 to January 2025， 108 elderly HFrEF patients were enrolled， with the mean age of （72.37 ± 6.54） years. Patients underwent a 6-month follow-up period， and the occurrence of major adverse cardiovascular events （MACE） was recorded. Clinical characteristics， hemodynamic parameters and myocardial microcirculation index were compared between MACE and non-MACE groups. Independent risk factors for MACE were identified using multivariate logistic regression， and receiver operating characteristic （ROC） curve was employed to assess predictive performance. Results During follow-up， 32 patients （29.63%） experienced MACE. Compared with the non-MACE group， the MACE group exhibited significantly higher age and atrial fibrillation incidence （P < 0.05）. The MACE group had lower PAPi but higher total myocardial ischemia burden and CSI scores than the non-MACE group （P < 0.05）. Multivariate logistic regression identified PAPi， total myocardial ischemia burden， and CSI score as independent predictors of MACE （P < 0.05）. ROC analysis showed that the combination of these 3 indicators achieved an area under the curve （AUC） of 0.948（95%CI： 0.888 - 0.982）， significantly higher than that of PAPi （AUC = 0.863， 95%CI： 0.784 - 0.922）， total myocardial ischemia burden （AUC = 0.914， 95%CI： 0.844 - 0.959）， CSI score （AUC = 0.760， 95%CI： 0.668 - 0.837） when used alone （all P < 0.05）. The combined test demonstrated a sensitivity of 84.37% and specificity of 96.05%. Conclusions PAPi， total myocardial ischemia burden and CSI score represent risk factors for MACE in elderly HFrEF patients. Their combined assessment provides high clinical value for predicting prognosis in this population.

Objective To investigate the predictive value of microRNA （miR）-155， miR-31-5p， Asprosin， and glycogen synthase kinase-3β （GSK-3β） levels in the development of osteoporosis （OP） in patients with type 2 diabetes mellitus （T2DM）. Methods A total of 158 patients diagnosed with T2DM and admitted to Shijiazhuang People's Hospital between March 2024 and October 2025 were selected as the research subjects. These patients were grouped according to the presence or absence of OP， which was determined based on the T-values from bone mineral density measurements. Patients with T-values ≤ -2.5 were classified into the T2DM-OP group （54 cases）， while the remaining patients were classified into the T2DM non-OP group （104 cases）. Multivariate factors associated with T2DM-OP were analyzed. Receiver operating characteristic （ROC） analysis was performed to assess the diagnostic efficacy of age， glycated hemoglobin （HbA_1C）， disease duration， smoking， drinking， miR-155， miR-31-5p， asprosin， and GSK-3β levels for T2DM-OP. Spearman correlation analysis was employed to explore the correlation between miR-155， miR-31-5p， asprosin， and GSK-3β levels and bone mineral density. Results The T2DM-OP group exhibited higher levels of age， HbA_1C， disease duration， miR-155， Asprosin， and GSK-3β when compared to the T2DM non-OP group. In contrast， the level of miR-31-5p in the T2DM-OP group was lower than that in the T2DM non-OP group. Moreover， the proportions of smoking and drinking were also higher in the T2DM-OP group than in the T2DM non-OP group （P < 0.05）. Age， HbA_1C， disease duration， smoking， drinking， miR-155， miR-31-5p， Asprosin， and GSK-3β were all identified as independent risk factors for T2DM complicated with OP （OR = 1.950， 1.876， 2.111， 2.008， 1.908， 2.002， 2.016， 1.793， 1.956， P < 0.05）. The combined detection of age， HbA_1C， disease duration， smoking， drinking， miR-155， miR-31-5p， Asprosin， and GSK-3β yielded an AUC value of 0.899 （95%CI： 0.848 - 0.949） for T2DM complicated with OP. The AUC values of each indicator detected individually were 0.805， 0.778， 0.829， 0.657， 0.651， 0.776， 0.759， 0.803， and 0.788 respectively. The AUC value of the combined detection was significantly higher than those of the individual detections （P < 0.05）. The sensitivity of the combined detection was 81.50% and the specificity was 86.50%. The levels of miR-155， Asprosin， and GSK-3β were negatively correlated with bone density （r = -0.612， -0.596， -0.604， P < 0.05）， whereas the level of miR-31-5p was positively correlated with bone density （r = 0.527， P < 0.05）. Conclusions Age， HbA_1C， disease duration， smoking， drinking， miR-155， miR-31-5p， Asprosin， and GSK-3β levels are all associated with T2DM complicated with OP. The combined detection of these indicators has a higher diagnostic efficacy than the individual detection of each indicator， and it is expected to provide new ideas for the early identification and prevention of high-risk patients.

Objective To investigate the therapeutic effect of a modified Wumei Pill in the treatment of diabetic gastroparesis （DGP） and its impact on insulin-like growth factor-1 （IGF-1） and transmembrane protein 16A （ANO1）， based on the theory of regulating both cold and heat conditions. Methods A total of 108 patients with DGP who were admitted to the Department of Traditional Chinese Medicine of Xuancheng People's Hospital from January 2022 to June 2025 were randomly divided into the control group （n = 54） and the Wumei Pill group （n = 54） by using a random number table. The control group received treatment with Mosapride Dispersible Tablets， whereas the Wumei Pill group was treated with Mosapride Dispersible Tablets plus modified Wumei Pill. The treatment course for both groups was 4 weeks. The clinical efficacy of the two groups after 4-week treatment was compared. The Traditional Chinese Medicine （TCM） syndrome score， intestinal flora， glucose metabolism， IGF-1， ANO1， gastrointestinal hormones， and gastric emptying levels were evaluated and compared respectively before treatment and 4 weeks after treatment. Meanwhile， the safety during the treatment period was recorded and compared. Results After 4 weeks of treatment， the total effective rate of the Wumei Pill group reached 88.89% （48/54）， which was significantly higher than that of the control group （72.22%， 39/54） （P < 0.05）. When compared with the pre - treatment status， after 4 weeks of treatment， the levels of serum pepsinogen Ⅰ （PG Ⅰ）， pepsinogen Ⅱ （PG Ⅱ）， and IGF-1， as well as the colony numbers of Bifidobacterium， Lactobacillus， and Bacteroides in fecal samples， increased in both groups. Moreover， these values were significantly higher in the Wumei Pills group （P < 0.05）. In comparison to the pre - treatment situation， after 4 weeks of treatment， the TCM syndrome scores （including epigastric fullness， acid reflux， and loose stools）， serum gastrin （GAS）， fasting blood glucose （FBG）， 2-hour postprandial blood glucose （2hPG）， ANO1 levels， and the colony numbers of Enterobacterium and yeast in fecal samples decreased in both groups. Notably， the levels in the Wumei Pill group were significantly lower （P < 0.05）. When compared with the pre-treatment period， the gastric emptying time of both groups was shortened after 4 weeks of treatment， and it was significantly shorter in the Wumei Pill group （P < 0.05）. Conclusions Based on mosapridi dispersive tablets， the application of modified Wumei Pills in the treatment of DGP using the cold-heat combined regulation method has a better therapeutic effect. It could regulate the expression of gastrointestinal hormones and intestinal flora， improve glucose metabolism， increase the level of IGF-1， reduce the level of ANO1， improve traditional Chinese medicine syndromes， and promote gastric emptying， with good safety.

Objective To observe the effects of preoperative ozone injection combined with high tibial osteotomy （HTO） on joint function， gait recovery， and serum inflammatory factors in patients with knee osteoarthritis （KOA）. Methods A total of 93 patients with KOA who underwent HTO in the hospital were retrospectively enrolled from March 2024 to March 2025. Based on the presence or absence of preoperative knee injection of ozone， they were divided into group A （injection， n = 47） and group B （non-injection， n = 46）. The changes in joint function， including the Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC）， Hospital for Special Surgery Knee Score （HSS score）， medial proximal tibial angle （MPTA）， and range of motion （ROM）， gait recovery （step length， walking speed， stride frequency）， and serum levels of Interleukin （IL）-1β， IL-6， IL-8， and IL-10 before and after treatment were compared between the two groups. Knee pain， as measured by the visual analogue scale （VAS）， was observed at 5 weeks， 1 month， and 6 months after surgery， and complications were recorded. Results At 5 weeks post-surgery， the WOMAC and MPTA in group A were lower than those in group B， whereas the HSS score and ROM were higher than those in group B （P < 0.05）. In the 120-meter gait test， the step length， walking speed， and stride frequency in group A were all higher than those in group B （P < 0.05）. The serum levels of IL-1β， IL-6， and IL-8 in group A were lower than those in group B， and the level of IL-10 was higher than that in group B （P < 0.05）. At 5 weeks， 1 month， and 6 months post-surgery， the Visual Analog Scale （VAS） scores in group A were lower than those in group B （P < 0.05）. There was no significant difference in the incidence of postoperative complications between the two groups （P > 0.05）. Conclusion Intra-knee injection of ozone can effectively promote the postoperative recovery of joint function and gait， alleviate the serum inflammatory response， and relieve postoperative pain in patients with KAO before HTO.

Objective To explore the relationship between non-suicidal self-injurious behavior， aggressive behavior， and sleep in children and adolescents with mood disorders， and to investigate whether there are differences in this relationship between the two genders， so as to improve the early intervention treatment for children and adolescents with mood disorders. Methods A total of 404 child and adolescent patients aged 10 - 19 who were diagnosed with mood disorders were collected from the Psychiatry Department of Huadu District People's Hospital in Guangzhou from January 2023 to January 2025. Self-rating scales were used to assess the clinical severity of the patients， including depressive symptoms， anxiety symptoms， sleep quality， and aggressive behavior. The outpatient doctors noted whether the patients had engaged in self-harming behavior in the past. Results Among all patients， the incidence of previous or current self-harm behavior was 60.64%. Among these self-harm patients， 85.71% were female. Among all pediatric and adolescent patients， there was a correlation between aggressive behavior and sleep. In female patients， this correlation was significant. In male patients， however， only sleep quality was inversely proportional to the score of physical aggression （r = -0.34， P = 0.043）. Conclusion Among children and adolescents with mood disorders， sleep is associated with aggressive behavior， and this association is more significant in females than in males， who also have a higher incidence of non-suicidal self-injurious behavior.

Objective To investigate the associations of the thyroid feedback quantile-based index （TFQI）， the thyroid-stimulating hormone index （TSHI）， the thyrotropin resistance index （TT4RI）， and the free triiodothyronine/free thyroxine （FT₃/FT₄） ratio with diabetic peripheral neuropathy （DPN） in patients with type 2 diabetes mellitus （T2DM）. Methods A total of 100 patients with T2DM who were admitted to the hospital from May 2022 to May 2025 were enrolled in this study. Based on the presence or absence of DPN， these patients were divided into the DPN group （n = 43） and the non-DPN group （n = 57）. Clinical data were collected， and thyroid hormone sensitivity indices were calculated. The influencing factors for DPN in T2DM were identified through univariate and multivariate logistic regression analyses. The relationship between thyroid hormone sensitivity indices and DPN was explored via Spearman correlation analysis. The predictive efficacy of these indices for DPN in T2DM was evaluated by using the receiver operating characteristic （ROC） curve. Results In comparison with the non-DPN group， the DPN group exhibited significantly lower levels of FT₃， TFQI， TSHI， TT4RI， FT₃/FT₄， motor conduction velocity （MCV）， and sensory conduction velocity （SCV）. Moreover， patients in the DPN group were older （P < 0.05）. Multivariate logistic regression analysis indicated that TFQI （OR = 0.491， 95%CI： 0.260 - 0.926）， TSHI （OR = 0.594， 95%CI： 0.387 - 0.911）， TT4RI （OR = 0.418， 95%CI： 0.183 - 0.954）， and FT₃/FT₄ （OR = 0.540， 95%CI： 0.352 - 0.827） were independent factors influencing the occurrence of DPN in T2DM （P < 0.05）. Spearman correlation analysis demonstrated that TFQI， TSHI， TT4RI， and FT₃/FT₄ were significantly negatively correlated with DPN （r = -0.563， -0.501， -0.541， -0.292， P < 0.05）. ROC curve analysis disclosed that the area under the curve （AUC）， specificity， and sensitivity of the combination of thyroid hormone sensitivity indices for predicting DPN in patients with T2DM were 0.918， 90.70%， and 93.00%， respectively. The AUC and sensitivity were significantly higher than those of TFQI， TSHI， TT4RI， or FT₃/FT₄ when used alone （P < 0.05）. Conclusions In patients with T2DM， a decreased sensitivity to thyroid hormone indices is closely related to the occurrence of DPN， and these indices are independent influencing factors for DPN. The combined detection of these indices can improve the predictive efficacy for DPN.

Pegylated interferon alpha （Peg-IFN-α） demonstrates dual antiviral and immunomodulatory properties， which allow a subset of chronic hepatitis B （CHB） patients to attain high hepatitis B surface antigen （HBsAg） clearance rates within a limited treatment period. This， in turn， presents the potential for clinical cure and a reduced risk of hepatocellular carcinoma. Nevertheless， its clinical application is restricted by high costs， significant adverse effects， and considerable inter-individual variability in therapeutic response. This highlights the need for accurate patient stratification. This review systematically assesses host-related factors （including age， gender， baseline alanine aminotransferase levels， interferon-related gene polymorphisms， and hepatic fibrosis status） and virological parameters （such as HBV genotype， viral mutations， viral load， and antigen/novel viral marker levels） that impact Peg-IFN-α treatment outcomes. By clarifying their predictive value and mechanistic roles， analyzing current therapeutic challenges， and suggesting individualized treatment strategies， this work aims to promote the optimization of clinical management protocols for CHB.

Objective This study utilized an in vitro differentiation model of human embryonic stem cells （hESCs） into cardiomyocytes （CMs） to establish an early heart development model. It was intended to assess the embryotoxicity of perfluorooctanesulfonic acid （PFOS） and the potential protective effect of vitamin D （VitD）. Methods hESCs were induced to differentiate using differentiation media containing either PFOS alone or a combination of PFOS and VitD. At the terminal stage （day 8） of cardiomyocyte differentiation， the differentiation process was observed under an optical microscope. Quantitative real - time reverse transcription polymerase chain reaction （RT-qPCR） was employed to detect the expression of myocardial differentiation marker proteins ［cardiac troponin T（cTNT）， α-actinin， NK2 homeobox 5 （NKX2.5）］ and mitochondrial complexes ［ubiquinol-cytochrome c reductase core protein 1 （UQCRC1）， cytochrome c oxidase subunit 2 （MTCO2）， ATP synthase subunit alpha （ATP5A1）］ on the 8th day. Mitochondrial metabolism during differentiation was evaluated by measuring the ATP levels and reactive oxygen species produced by mitochondria on the 2nd day. Results The results clearly indicated that exposure to PFOS significantly inhibited the differentiation capacity of hESCs into CMs. This toxic effect was strongly associated with mitochondrial dysfunction， whereas VitD showed the potential to counteract this toxicity. In comparison with the control group， the density of mature cardiomyocyte colonies was notably reduced in the PFOS-exposed group. Nevertheless， in the group treated with both PFOS and VitD， the colony density was restored to a level approaching that of the control. Moreover， RT-qPCR results demonstrated that VitD effectively mitigated the PFOS-induced decrease in the expression of cardiomyocyte differentiation markers. Mitochondrial function tests further disclosed that PFOS exposure resulted in a substantial decline in mitochondrial energy metabolism efficiency in CMs derived from hESCs， triggered oxidative stress， and impaired normal mitochondrial function. These effects were reversed to normal levels after co-intervention with VitD. Conclusions The findings clearly demonstrated that PFOS inhibited the differentiation of hESCs into CMs. VitD could effectively counteract the toxic effects induced by PFOS and restore mitochondrial function via the regulation of mitochondrial-related signaling pathways.

Objective This study investigates the mechanism of combination therapy of Regorafenib and Irinotecan in hepatocellular carcinoma under hypoxic conditions and aims to provide a new therapeutic strategy for anticancer drugs combination to improve outcomes. Methods The median inhibitory concentration （IC₅₀） of drugs against hepatocellular carcinoma cells under normoxic and hypoxic conditions were determined， dose-response curves were plotted to evaluate the sensitivity to Oxaliplatin Regorafenib and Irinotecan. Combined effects of different concentrations of Regorafenib and Irinotecan on hepatocellular carcinoma cells were analyzed using CompuSyn and SynergyFinder 3.0 software. The impacts on cell death rates were determined via flow cytometry. The effects on cell proliferation were determined using EdU proliferation assays. The influences on cell migration were assessed through Transwell and wound healing assays. The alterations of relevant proteins in signaling pathways were detected by Western blot experiments. Results Hypoxia had no significant effect on the IC₅₀ values of Regorafenib and Irinotecan. Compared to Oxaliplatin， both agents can overcome hypoxia-induced treatment tolerance. Under hypoxic conditions， Regorafenib and Irinotecan exhibited synergistic effects with a combination index （CI values） < 1 and a ZIP synergy score > 10. Compared to regorafenib and irinotecan groups， the combination of Regorafenib and Irinotecan significantly increased the cells proportion in SubG1 phase （P < 0.000 1） and exhibited combined inhibitory effects on cell migration （P < 0.000 1）. Under hypoxic conditions， Irinotecan increased the proportion of proliferating cells （P < 0.000 1）， which significantly decreased upon combination with Regorafenib （P < 0.000 1）， accompanied by reduced intracellular CyclinD1 levels （P < 0.000 1） Under hypoxic conditions， Irinotecan upregulated HIF-1α expression and activated ERK1/2 signaling （P < 0.000 1）， combination with Regorafenib modulated Irinotecan-mediated expression or activation （P < 0.000 1）， and the combination therapy downregulated AKT and ERK1/2 signaling activity （P < 0.001）. Conclusions Under hypoxic conditions， the combination of Regorafenib and Irinotecan overcomes hypoxia-induced treatment tolerance， promotes hepatocellular carcinoma cell death， and inhibits hepatocellular carcinoma cell proliferation and migration. This synergistic effect may be associated with the suppression of HIF-1α and CyclinD1 expression， as well as the downregulation of AKT and ERK1/2 phosphorylation levels in hepatocellular carcinoma cells.

Objective To investigate the dynamic changes of immune cell subsets in a mouse model of pulmonary hypertension （PH） induced by Sugen-hypoxia （SuHx）. Methods A SuHx-PH mouse model was established through intraperitoneal injection of Sugen 5416， followed by exposure to hypoxia. Mouse lung tissues were collected prior to modeling and at 1 week （h1w）， 2 weeks （h2w）， 3 weeks （h3w）， and 4 weeks （h4w） post-modeling. Flow cytometry was employed to detect the proportional alterations of immune cell subsets （including T cells， B cells， macrophages， eosinophils （EOS）， neutrophils （Neu）， natural killer （NK） cells， and innate lymphoid cells （ILCs） within CD45⁺ immune cells. Results Compared with the control group， the immune cell subsets in SuHx model mice demonstrated significant temporal changes. Among these， the total CD11c⁺F4/80⁺ macrophages and interstitial macrophages （IM， SIGLECF^-） showed a significant decreasing tendency as the modeling time progressed； the cell levels of alveolar macrophages （AM， SIGLECF⁺） continuously increased （P < 0.05）； EOS， ILCs， Neu， and CD4⁺T cells displayed a significant fluctuating pattern， with significant differences between groups （P < 0.05）. Conclusions The proportions of immune cell subsets in the lung tissues of SuHx-PH mice exhibit significant temporal changes， indicating that different immune cells may play stage-specific roles in the progression of PH. This study offers a foundation for a more in-depth understanding of the immunoinflammatory mechanism of PH and the identification of potential immune intervention targets.

Objective To investigate the association between genetic variants in the promoter region of the PDE4D gene and the risk of intrauterine adhesions in patients following curettage abortion. Methods This study conducted genotyping of two polymorphisms， rs7701573 and rs997421， in 113 patients diagnosed with intrauterine adhesions and 270 control subjects from the hospital who underwent curettage abortions between 2022 and 2023. Subsequently， we employed multiple logistic regression models to analyze their association with the risks of intrauterine adhesions. Results Individuals with rs997421 CT+TT genotypes had a lower risk of intrauterine adhesions （adjusted OR = 0.635， 95%CI： 0.408 - 0.988） compared to those with the rs997421 CC genotype. The protective effect was more pronounced in patients with more extensive cavity involvement of adhesions （adjusted OR = 0.518， 95%CI： 0.268 - 0.999） and in those with fibrous （Firm & Dense） adhesions （adjusted OR = 0.596， 95%CI： 0.371 - 0.956）. However， the rs7701573 polymorphism did not significantly affect the risk of intrauterine adhesions. To our knowledge， this study is the first to report the association between PDE4D gene polymorphisms and the risk of intrauterine adhesions after curettage abortion. Conclusions This study first indicates that the rs997421 polymorphism with the CT+TT genotype is associated with a reduced， protective risk of intrauterine adhesions， especially in patients with fibrous adhesions and extensive uterine cavity involvement. This provides new perspectives for preventing intrauterine adhesions after curettage abortion.

Objective To explore the mediating effect of sleep quality on the relationship between cerebral small vessel disease （CSVD） and cognitive function among the older adults in Nantong. Methods A total of 412 patients aged 60 years or above with CSVD admitted to the Department of Nantong First People's Hospital in Nantong from March 2024 to March 2025 were enrolled in this retrospective study. Based on the cognitive function assessed by the Montreal Cognitive Assessment （MoCA）， patients were divided into the cognitive impairment （CI） group and the non-CI group for comparison. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index （PSQI）. Multiple linear regression analysis was conducted to determine the relationships among key variables. The mediating effect of sleep quality between CSVD and cognitive function was analyzed using Model 4 of the PROCESS macro version 4.1， and the mediating effect was validated through the Bootstrap method. Results There were 192 patients （46.6%） with CI， and 220 patients （53.4%） without CI. Patients in the CI group presented a greater burden of CSVD， higher proportions of lacunes， moderate-to-severe white matter hyperintensities （WMH）， cerebral microbleed （CMB）， and basal ganglia-enlarged perivascular spaces （BG-EPVS） exceeding 10， as well as elevated PSQI scores compared to the non-CI group. All these differences were statistically significant （all P < 0.05 or P < 0.001）. After adjusting for covariates such as age， sex， years of education， Hamilton Anxiety Scale （HAMA） scores， Hamilton Depression Rating Scale-17 （HAMD-17） scores， and vascular risk factors， the CSVD burden， the number of lacunes， the number of CMB， the number of BG-EPVS， and the severity of WMH were all significantly negatively correlated with Montreal Cognitive Assessment （MoCA） scores （all P < 0.001）， and significantly positively correlated with PSQI scores （all P < 0.05 or P < 0.001）. Additionally， PSQI scores were significantly negatively correlated with MoCA scores （P < 0.001）. Mediated effect analysis indicated that sleep quality plays a partial mediating role in the relationship between CSVD and cognitive function. The mediating effect ratios in the relationships between CSVD burden， lacunes， WMH， CMB， BG-EPVS and cognitive function are 15.2%， 15.8%， 21.7%， 16.7% and 23.0% respectively. In the Bootstrap test （5 000 times）， neither the upper nor the lower limit of the 95% confidence interval contains 0， suggesting that the mediating effect is significant. Conclusions Sleep quality plays a partial mediating role in the process by which CSVD leads to CI among the elderly in Nantong. Enhancing sleep quality may be beneficial in reducing the risk of developing CSVD-CI.

Objective To investigate the predictive value of serum soluble CD276 （sCD276）， chitinase-3-like protein 1 （YKL-40）， microRNA （miR）-152-5p and miR-193a-5p in patients with high-grade serous ovarian cancer （HGSOC）. Methods A total of 240 patients with HGSOC admitted to the Department of Gynecology， Wuhan Hospital of Integrated Traditional Chinese and Western Medicine from October 2018 to October 2022 were selected as the study subjects. All selected patients received standard initial therapy and underwent regular follow-up for 3 years starting after completion of initial treatment. Follow-up continued until patient death or October 31， 2025. Among the 240 enrolled patients， 4 were excluded due to loss to follow-up， resulting in 236 patients included in the study. Based on 3-year follow-up records， patients were divided into poor prognosis group （71 cases） and good prognosis group （165 cases）. Clinical data and serum levels of sCD276， YKL-40， miR-152-5p， and miR-193a-5p in the poor prognosis and good prognosis groups were compared. The risk factors for poor prognosis in patients with HGSOC were analyzed. The predictive value of serum levels of sCD276， YKL-40， miR-152-5p， and miR-193a-5p in patients with HGSOC was assessed by ROC curves. Results The proportion of ascites， lymph node metastasis， and postoperative residual disease and serum levels of sCD276 and YKL-40 in the poor prognosis group were higher than the good prognosis group （P < 0.05）， serum levels of miR-152-5p and miR-193a-5p were lower than the good prognosis group （P < 0.05）. Ascites， lymph node metastasis， postoperative residual lesions and high levels of serum sCD276 and YKL-40 were independent risk factors for poor prognosis in patients with HGSOC （P < 0.05）， while high levels of serum miR-152-5p and miR-193a-5p were protective factors （P < 0.05）. ROC analysis revealed that the combined detection of serum sCD276， YKL-40， miR-152-5p， and miR-193a-5p in predicting the prognosis of HGSOC patients was 0.895， with a sensitivity of 88.73% and specificity of 73.33%， the combined detection AUC significantly exceeded that of individual markers （P < 0.05）. Conclusions The serum levels of sCD276 and YKL-40 in patients with poor prognosis of HGSOC were highly expressed， while the serum levels of miR-152-5p and miR-193a-5p were lowly expressed. Ascites， lymph node metastasis， postoperative residual lesions and serum levels of sCD276， YKL-40， miR-152-5p and miR-193a-5p were closely related to the prognosis of patients， and the combined detection of serum levels of sCD276， YKL-40， miR-152-5p and miR-193a-5p was more valuable in predicting the prognosis of patients with HGSOC.

Objective To construct and validate a nomogram model for predicting the risk of central precocious puberty （CPP） in girls with early breast development， to establish a quantifiable and visual dynamic risk assessment tool and provide evidence-based support for the selecting the timing of individualized intervention. Methods A total of 162 girls with early breast development who visited the Pediatrics Department of Hebei Provincial People's Hospital from September 2023 to December 2024 were retrospectively included. Based on pubertal development status and the results of the gonadotropin-releasing hormone stimulation test， the subjects were divided into an isolated premature thelarche （IPT） group （59 cases） and the CPP group （103 cases）. Clinical data were compared between the two groups. Predictors were screened using binary logistic regression and LASSO regression. A nomogram model was constructed， and its performance was evaluated using the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. Results Statistical analysis revealed significant differences between the two groups in height standard deviation score， weight standard deviation score， bone age， bone age advancement， bone age index， the number of follicles greater than 4 mm， uterine volume， estradiol， insulin-like growth factor 1 （IGF-1）， basal luteinizing hormone （LH） level， basal follicle-stimulating hormone （FSH） level， LH/FSH ratio， LH peak， FSH peak， and LH peak/FSH peak ratio （P < 0.05）. Four independent predictors of basal LH level， height standard deviation score， IGF-1， and the number of follicles greater than 4mm were screened out. The nomogram model showed an AUC of 0.932， at a probability threshold of 0.414，the sensitivity was 95.1%， the specificity was 78.0%， the model demonstrated good calibration and the clinical net benefit rate was 54.6%. Conclusions The nomogram model incorporating basal LH level， height standard deviation score， IGF-1 and the number of follicles greater than 4mm can effectively predict the risk of central precocious puberty in girls with early breast development. It provides a practical tool for non-invasive screening and facilitates early clinical intervention.

Objective To explore the predictive value of pregnancy-associated plasma protein A （PAPP-A） combined with thyroid peroxidase antibody （TPO-Ab） for pregnancy outcomes in patients with subclinical hypothyroidism complicated with gestational hypertension. Methods A total of 186 pregnant women with subclinical hypothyroidism admitted to the hospital from January 2020 to January 2025 were selected. They were divided into the subclinical hypothyroidism group （n = 87） and the subclinical hypothyroidism combined with gestational hypertension group （n = 99） based on the presence of gestational hypertension. Meanwhile， 102 normal pregnant women during the same period were enrolled as the control group. Basic data of all pregnant women were collected， and their serum levels of PAPP-A and TPO-Ab were detected. The occurrence of adverse pregnancy outcomes such as abortion， preterm birth， and postpartum hemorrhage in the subclinical hypothyroidism combined with gestational hypertension group was followed up and recorded. Logistic regression analysis was used to screen the risk factors for adverse pregnancy outcomes， and ROC curves were employed to evaluate the predictive value of serum PAPP-A and TPO-Ab levels for pregnancy outcomes. Results The serum PAPP-A level in the subclinical hypothyroidism combined with gestational hypertension group was lower than that in the subclinical hypothyroidism group and the control group， while the TPO-Ab level was higher， with statistically significant differences （P < 0.05）. Follow-up results showed that 46.46% （46/99） of the 99 pregnant women in the subclinical hypothyroidism combined with gestational hypertension group had adverse outcomes. Multivariate analysis indicated that elevated TPO-Ab and decreased PAPP-A were risk factors for adverse pregnancy outcomes （P < 0.05）. ROC curve analysis revealed that the combination of PAPP-A and TPO-Ab had high accuracy in evaluating the pregnancy outcomes of the patients. Conclusion Decreased PAPP-A and elevated TPO-Ab are risk factors for adverse pregnancy outcomes in patients with subclinical hypothyroidism complicated with gestational hypertension， and their combination has high predictive value for the pregnancy outcomes of such patients.

Objective To evaluate the predictive value of embryo dynamics parameters during embryo time-lapse imaging technique on embryo implantation potential in patients receiving in vitro fertilization-embryo transfer （IVF-ET） assisted pregnancy. Methods A total of 292 patients who underwent IVF-ET assisted pregnancy at Nanyang First People's Hospital between June 2022 and June 2024 were selected as study subjects. After 28 days of transplantation， the patients were divided into 103 cases in implantation group and 189 cases in non-implantation group based on the embryo implantation status detected by B-ultrasound. The basic data and embryo dynamics parameters of the patients in each group were compared. Multivariate logistic regression analysis was conducted to identify high-risk factors for embryo non-implantation in patients with IVF-ET assisted pregnancy. Subsequently， the predictive value of these high-risk factors on embryo implantation potential was evaluated by using receiver operating characteristic （ROC） curve. Results Compared with implantation group， the embryo dynamics parameters in non-implantation group were higher， including the time of pronuclear breakdown to 2-cell stage （t2）， time of pronuclear breakdown to 3-cell stage （t3）， time of pronuclear breakdown to 4-cell stage （t4）， time of 2-cell division to 3-cell stage （cc2）， time of 3-cell division to 4-cell stage （s2）， and time of 4-cell division to 5-cell stage （cc3） （P < 0.05）. t2 （OR = 4.293）， t3 （OR = 0.507）， t4 （OR = 5.534） and s2 （OR = 3.755） were independent risk factors for embryo non-implantation in patients with IVF-ET assisted pregnancy （P < 0.05）. t2， t3， t4 and s2 had high predictive efficiency on embryo implantation failure in patients with IVF-ET assisted pregnancy， and their areas under the curves （AUCs） were 0.767， 0.744， 0.720 and 0.878 respectively （P < 0.05）， and the efficiency of s2 in predicting embryo non-implantation in patients with IVF-ET assisted pregnancy was higher than that of t2， t3 or t4 （Z = 3.044， 3.563， 4.413， P < 0.05）. Conclusions The levels of embryo dynamics parameters t2， t3， t4 and s2 are closely related to the embryo implantation in patients with IVF-ET assisted pregnancy. The use of embryo time-lapse imaging technique can assist medical staff in predicting the embryo implantation potential in patients with IVF-ET assisted pregnancy.

Objective To investigate the association between the Geriatric Nutritional Risk Index （GNRI） and the prognosis of patients with erythroderma， and to assess its effectiveness in predicting adverse outcomes， thus providing a basis for nutrition risk stratification and management. Methods A total of 183 hospitalized patients aged ≥ 60 years with erythroderma from the Guangdong Provincial Hospital of Chinese Medicine between August 2017 and October 2024 were recruited. Clinical data were gathered， and the GNRI was computed. The subjects were classified into a no nutritional risk group （n = 78）， a mild nutritional risk group （n = 39）， and a moderate-to-severe nutritional risk group （n = 66） according to their GNRI. A generalized linear model was employed to analyze the association between the GNRI and prognosis， and receiver operating characteristic （ROC） curves were drawn to assess the predictive performance of the GNRI for prognosis. Results The moderate-to-severe nutritional risk group exhibited a significantly elevated risk of infection （OR = 4.81， 95%CI： 1.54 - 15.99， P = 0.007）. Specifically， there was a higher risk of pulmonary infection （OR = 8.00， 95%CI： 1.01-63.28， P = 0.049）， and a significantly extended hospital stay （β = 2.53， 95%CI： 0.96 - 4.10， P = 0.002）. The area under the curve （AUC） of GNRI for predicting infection in patients with erythroderma was 0.71 （95%CI： 0.61 - 0.81）， and the AUC for predicting pulmonary infection was 0.81 （95%CI： 0.65 - 0.96）. Conclusions The GNRI serves as an effective indicator for predicting infections， especially pulmonary infections， among elderly patients suffering from erythroderma. Moderate-to-severe nutritional risk is notably correlated with elevated infection rates and extended hospital stays. Consequently， it is advisable to adopt the GNRI as a routine nutritional screening tool for elderly erythroderma patients and to carry out early interventions based on risk stratification to enhance clinical outcomes.

Objective To investigate the efficacy of fire needling combined with pulsed laser and erythromycin ointment in treating cystic acne， as well as its impact on the levels of serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）， and skin lesions. Methods A total of 204 patients diagnosed with cystic acne and admitted to the Geriatric Hospital Affiliated to Wuhan University of Science and Technology between July 2022 and December 2023 were included in this study. By using a random number table method， they were divided into four groups： the control group， which received fire-needling treatment； combination group 1， treated with fire needling plus pulsed laser； combination group 2， treated with fire needling plus erythromycin ointment； and combination group 3， treated with fire needling， pulsed laser， and erythromycin ointment. With a treatment course of one month， all groups underwent three courses of treatment. Propensity score matching （PSM） was employed to match the clinical data at a ratio of 1∶1∶1∶1. The efficacy， sex hormone levels before and after treatment， severity of skin lesions， skin barrier function， and adverse reactions were compared among the groups. Results Before PSM， a total of 204 patients were included in the study， with 51 cases allocated to each group. After PSM， each group was composed of 40 patients， and their baseline data were comparable （P > 0.05）. There were significant differences in the clinical effective rates among the groups. Specifically， the effective rate in combination group 3 was 92.50%， which was significantly higher than that in the control group （65.00%） and combination group 2 （75.00%） （P < 0.05）. Nevertheless， there was no statistical difference when compared with combination group 1 （85.00%）. After treatment， the serum levels of FSH， LH， and E2 increased in all groups. Among them， combination group 3 showed the highest levels of these hormones （P < 0.05）. Additionally， the skin lesion scores of all groups decreased after treatment， and combination group 3 had the lowest scores （P < 0.05）. Regarding skin physiological parameters， after treatment， the stratum corneum water content increased in all groups， whereas the transepidermal water loss （TEWL）， the content of mucins and proteins related to desquamation， and skin erythema （a value） decreased. Combination group 3 had a higher stratum corneum water content than the control group， lower TEWL than the control group and combination group 2， a lower a value than the other three groups， and lower content of mucins and proteins related to desquamation than the control group （P < 0.05）. The adverse reactions that occurred during treatment included itching， redness， swelling， and mild bleeding. The incidence of adverse reactions in combination group 3 was the highest， reaching 20.00%. However， there was no significant difference in the incidence of adverse reactions among the four groups （P > 0.05）. Conclusions The combined use of fire needling， pulsed laser， and erythromycin ointment is effective in treating cystic acne. It can improve patients' sex hormone levels and skin lesions without a significant increase in adverse reactions， which demonstrates favorable clinical application value.

Objective To analyze the risk factors for cerebral infarction after surgery for intertrochanteric fracture of the femur （IFF） among elderly patients and establish a decision-tree risk prediction model， so as to provide a scientific theoretical basis for clinical medical staff to formulate targeted prevention and treatment plans. Methods Clinical data of 215 elderly patients who underwent surgery for IFF at our hospital from November 2017 to December 2023 were retrospectively selected. The patients were divided into the cerebral infarction group and the non-cerebral infarction group according to the postoperative occurrence of cerebral infarction. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for cerebral infarction after IFF surgery in elderly patients. A decision tree model and logistic regression were utilized to construct a risk prediction model， and the predictive values of both models for cerebral infarction after IFF surgery were compared. Results Among the 215 elderly patients who underwent surgery for IFF， 61 suffered from cerebral infarction post-operatively， with an incidence rate of 28.37%. Multivariate logistic regression analysis indicated that hypertension， diabetes， the duration of hospital bed rest， homocysteine， and D-dimer were risk factors for cerebral infarction after IFF surgery in elderly patients， while quality nursing was identified as a protective factor （P < 0.05）. A decision tree model was constructed based on these risk factors， with diabetes， the duration of hospital bed rest， Hcy， D-D， and quality nursing selected as explanatory variables. The model had a total of 4 layers and 15 nodes. The duration of hospital bed rest was the most significant influencing factor for cerebral infarction after IFF surgery in elderly patients. The area under the curve （AUC） value of the decision tree model for cerebral infarction after IFF surgery in elderly patients was 0.964 （95%CI： 0.930 - 0.985）， whereas the AUC value of the logistic regression model was 0.896 （95%CI： 0.847 - 0.933）. The DeLong test result for the two models was Z = 3.401， P = 0.000 7. Conclusions Hypertension， diabetes， the duration of hospital bed rest， Hcy， and D-D are identified as risk factors for cerebral infarction after IFF surgery in elderly patients， while quality nursing is recognized as a protective factor. The decision tree risk prediction model constructed based on these risk factors demonstrates significantly higher predictive efficacy compared to the logistic regression model.

Postoperative delirium （POD） exhibits a relatively high incidence among patients undergoing liver surgery， especially after liver transplantation. Risk factors， including preoperative hepatic insufficiency， intraoperative hepatic ischemia-reperfusion injury， and postoperative sleep deprivation， contribute to the occurrence of POD in liver surgery by influencing neuroimmunity. Dexmedetomidine （DEX） can directly disrupt neuroimmune circuits via its anti-inflammatory， anti-oxidant， and anti-apoptotic effects. Moreover， it can also optimize the neuroimmune microenvironment by enhancing the glymphatic system， enhancing sleep quality， and facilitating neuronal proliferation， ultimately decreasing the incidence of POD. This article intends to systematically review the mechanisms and clinical application of DEX in reducing the incidence of POD after liver surgery by modulating neuroimmunity through mitigating inflammatory responses and reinforcing neuroprotection.