ObjectiveTo investigate the effects of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） gene G501C on brain structure and cognitive function in patients with white matter hyperintensities （WMH）. MethodsA total of 118 patients with WMH were enrolled. All participants underwent T1-weighted and T2-fluid-attenuated inversion recovery （T2-FLAIR） MRI to assess gray matter structure and WMH burden， and completed the mini-mental state examination （MMSE） and Montreal cognitive assessment （MoCA）. Partial correlation and mediation analyses were performed to explore the impact of LOX-1 polymorphism on cognitive function. ResultsParticipants were divided into GG+GC group （n = 35） and CC group （n = 83）. The GG+GC group showed lower MMSE and MoCA scores （MMSE： P=0.003； MOCA： P=0.015）， as well as greater WMH burden （all P0.001）， compared with the CC group. Voxel-based morphometry （VBM） analysis revealed reduced left thalamic volume in the GG+GC group， which was correlated with cognitive scores （all P0.05）. Subregional thalamic analysis further showed volume reductions in the lateral， ventral， medial， and pulvinar thalamic regions （all P0.05） in the GG+GC group， all positively associated with cognitive performance （all P0.05）. Mediation analyses indicated that volumes of the medial and pulvinar thalamic regions mediated the association between genotype and cognitive function （MMSE， MoCA）， and that WMH volume mediated the effect on MoCA scores. ConclusionThe LOX-1 G501C polymorphism may indirectly affect cognitive function by influencing specific thalamic subregional volumes and white matter damage， suggesting a potential mediating role of thalamic structures between genetic background and cognitive impairment.

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

[Objective]To investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A(IDH3A)on cardiomyocyte hypertrophy.[Methods]The expression of IDH3A in the myocardium of healthy volunteers(n=10)and patients with heart failure(HF)(n=10),and in the myocardium of mice subjected to transverse aortic constriction(TAC)surgery and sham operation,as well as in phenylephrine(PE)-induced neonatal rat ventricular cardiomyocytes(NRVCs),was assessed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot assay.The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated.The effect of IDH3A on NRVCs area was examined by phalloidin staining assay.A mutant of IDH3A with abolished enzymatic activity,IDH3A_D208A,was generated through site-directed mutagenesis.The impact of this IDH3A mutant on the hypertrophic phenotype,ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity.The effect of exogenous α-ketoglutaric acid(AKG)on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay,respectively.[Results]IDH3A was significantly decreased in the myocardium of HF patients,in the myocardium of TAC-operated mice,and in PE-induced NRVCs(P=0.005 2,P=0.026 6,P=0.041 3 and P=0.006 6,respectively).Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs(P<0.000 1,P=0.000 1 and P=0.000 2,respectively).The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs(P=0.001 2 and P<0.000 1,respectively),whereas the enzymatically inactive IDH3A mutant lacked this effect.Exogenous AKG provision could,but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy.[Conclusion]IDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level,providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

Objective:To explore the impacts of different frequencies of orthogonal image-guided verification on set-up error correction and the reference values of planning target volume (PTV) margins in postoperative radiotherapy for breast cancer, in order to provide recommendations of the verification frequency in clinical practice.Methods:A total of 80 breast cancer patients who received postoperative intensity-modulated radiotherapy for breast cancer at the Affiliated Union Hospital of Fujian Medical University from January 2021 to January 2022 were enrolled. Orthogonal image-guided verification was conducted before each radiation treatment to determine initial and residual set-up errors. The error data were statistically analyzed by categorizing patients into groups A, B, C, D, E, and F, based on assumed verification frequencies (daily, every 2, 3, 4, and 5 d, and no correction). The magnitude, distribution, and differences of set-up errors of various groups were analyzed, and the PTV margins were calculated using a reference formula.Results:The collected initial set-up errors of the 80 patients were (3.49±3.43), (2.87±2.88), and (2.75±2.35) mm, in x, y, and z directions, respectively. The residual set-up errors decreased gradually with increasing verification frequency. In the case of daily image-guided verification, the residual set-up errors in x, y, and z directions decreased to (1.63±0.90), (1.63±0.93), and (1.55±0.90)mm, respectively. The reference values of PTV margins calculated under different verification frequencies decreased with an increase in the verification frequency. Under daily verification, the reference values of PTV margins calculated based on set-up errors decreased from initial 6.60, 6.29, and 4.22 mm (without correction) to 1.27, 1.37, and 1.28 mm, respectively. Differences in the reference values under verification frequencies every 3, 4, and 5 d were less than 0.81 mm. Conclusions:Daily image-guided verification (including correction) can effectively reduce set-up errors in image-guided radiotherapy for breast cancer. The set-up errors differ under varying verification frequencies, with a higher frequency corresponding to better correction effects and smaller PTV margins required.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.

Objective To compare the clinical efficacy of the transforaminal endoscopic lumbar discectomy(TELD)approach with that of the interlaminar endoscopic lumbar discectomy(IELD)approach,both performed using a single-channel spinal endoscope,in the treatment of L4-L5 degenerative lumbar lateral recess stenosis(DLLRS).Methods A retrospective analysis was conducted on 78 patients with L4-L5 DLLRS who underwent single-channel endoscopic spinal surgery at our institution between March 2020 and March 2024.Patients were classified into the TELD group(lateral transforaminal approach,n=34)and the IELD group(interlaminar approach,n=44).Propensity score matching(PSM)was performed in a 1∶1 ratio using age,sex,body mass index(BMI),and duration of symptoms as covariates,yielding 25 matched pairs for final comparative analysis.Perioperative outcomes were systematically compared between groups.Visual analog scale(VAS)scores for low back pain and leg pain,as well as the Oswestry Disability Index(ODI),were evaluated preoperatively and at 3 days,3 months,6 months,and 1 year postoperatively.Lumbar computed tomography(CT)scans obtained 3 days after surgery were used to measure the lateral recess angle(LRA)and assess the extent of decompression.Spinal stability was evaluated using dynamic lumbar radiographs at 3 months postoperatively.Clinical outcomes were assessed 1 year after surgery based on the modified MacNab criteria.Results Both groups showed significant reductions in VAS scores for low back and leg pain,as well as in ODI scores,at all postoperative time points compared to baseline values(P<0.05).However,no statistically significant differences were observed between the two groups(P>0.05).Lumbar CT scans performed on postoperative day 3 demonstrated a significant increase in LRA in both groups relative to preoperative measurements(P<0.05).Although the magnitude of increase was greater in the IELD group,the intergroup difference did not reach statistical significance(P>0.05).At 3 months postoperatively,dynamic lumbar radiographs revealed no deterioration in spinal stability in either group compared to preoperative conditions,with no significant difference between groups(P>0.05).According to the modified MacNab criteria at 1 year postoperatively,the excellent and good outcome rate was 88.0%in the TELD group and 92.0%in the IELD group,with no statistically significant difference between the groups(P>0.05).Conclusions Both the TELD and IELD techniques are safe and effective for managing L4-L5 DLLRS,yielding comparable clini-cal outcomes.The selection of surgical approach should be guided by the anatomical location of ventral disc protru-sions,as well as the degree of facet joint hypertrophy and neural compression.

Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.