Objective To systematically evaluate the similarities between six-gene-modified pig red blood cells and human red blood cells in multiple dimensions, including cell morphology, hematological parameters, microbial safety and serological compatibility, and to verify the feasibility of using six-gene-modified pig red blood cells as an alternative for blood transfusion in cases of traumatic hemorrhage. Methods Blood samples from O-type human donor, six-gene-modified O-type pig and wild-type O-type pig were collected. The pig gene-modified phenotype was identified by flow cytometry. The morphology was observed using field emission scanning electron microscopy and the diameter was measured. Hematological tests, including blood routine, osmotic fragility test, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) content and partial pressure of oxygen at 50% hemoglobin saturation (P50), were conducted to assess the deformability of red blood cells. Real-time fluorescent quantitative polymerase chain reaction was used to screen for zoonotic viruses, and cross-matching was performed using column gel method, condensation amine method and saline tube method. Results The six-gene-modified pig red blood cells successfully knocked out the α-Gal, Neu5Gc and Sda antigens and expressed hCD55. Wild-type pig red blood cells expressed these three antigens but did not express human complement regulatory proteins. All three types of red blood cells presented a biconcave discoid morphology. The diameter of O-type human red blood cells was larger than that of the six-gene-modified porcine red blood cells and wild-type pig red blood cells (all P < 0.05). The average red blood cell volume and average red blood cell hemoglobin of O-type humans were higher than those of the six-gene-modified pig red blood cells, and the distribution width-variable coefficient of O-type human red blood cells was lower than that of the six-gene-modified pig red blood cells (all P < 0.05). There were no statistically significant differences in the permeability fragility, ATP content, 2,3-DPG content, P50 and red blood cell deformability indicators of the three types of red blood cells (all P > 0.05). The screening for zoonotic viruses in human and animal cells of the six-gene-modified pigs and wild-type pigs was negative. The cross-matching results showed that in the column gel method and condensation amine method, the primary and secondary sides of the six-gene-modified pig red blood cells did not agglutinate with human red blood cells, while the wild-type pig red blood cells agglutinated with human red blood cells in all cross-matching methods. Conclusions The six-gene-modified pig red blood cells are highly similar to human red blood cells in terms of morphology, key hematological parameters, energy metabolism, oxygen-carrying capacity, mechanical properties, microbial safety and serological compatibility, providing an experimental basis for the clinical transformation of xenotransfusion.

Objective To observe the feasibility of transesophageal echocardiography(TEE)combined with agitated saline contrast echocardiography(ASCE)for identifying morphological characteristics of high-risk patent foramen ovale(PFO)and evaluating the risk of PFO related stroke.Methods Totally 212 PFO patients diagnosed by TEE combined with ASCE were enrolled,including 100 cases with cryptogenic stroke(CS)(CS group)and 112 without CS(non-CS group).Anatomical morphological characteristics of PFO were comparatively analyzed between groups to screen the independent factors of CS.Results In CS group,the left and right atrial opening diameters of PFO were all larger than those in non-CS group in both resting-state and stimulated state.The aortic root diameter in CS group was larger than that in non-CS group,and the incidence of atrial septal aneurysm(ASA),high activity of the atrial septum,inferior vena cava valve or Chiari network,large amount of right-to-left-shunt(RLS)in stimulated state,and multiple outlets of the oval valve in CS group were all higher than those in non-CS group(all P＜0.05).Logistic regression analysis showed that ASA,high atrial septal activity,large amount of RLS and multiple oval valve outlets were all independent factors associated with CS(OR=0.211,0.384,0.999,0.199,all P＜0.05).Conclusion TEE combined with ASCE could identify anatomical characteristics of high-risk PFO and assess the risk of PFO related stroke.

Objective:To evaluate the efficacy of almonertinib,a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI),as a first-line treatment for patients with EGFR-mutated advanced non-small cell lung cancer(NSCLC)in the real-world clinical practise,and to systematically analyze the independent risk factors influencing their prognosis.Methods:This retrospective cohort study enrolled 73 patients with EGFR-mutated advanced NSCLC who received first-line treatment with aumolertinib from April 1,2020 to December 31,2021.Survival curves were generated by using the Kaplan-Meier method,and intergroup comparisons were performed via log-rank test.Univariate and multivariate analyses of prognostic factors were conducted by using the COX proportional hazards regression model,with a focus on identifying prognostic factors in the subgroup of baseline brain metastases.Results:Among 73 patients,the median progression-free survival(mPFS)was 19.4 months,and the disease control rate(DCR)was 93.2%.Multivariate COX regression analysis revealed that central nervous system(CNS)metastasis status,EGFR mutation subtype,ECOG performance status(PS)score,and gender might be independent risk factors for PFS.Among 33 patients with baseline brain metastases,combined almonertinib with radiotherapy or bevacizumab,maximum diameter of brain metastases(≥3 cm),and ECOG PS score might be independent risk factors of PFS.Conclusion:This first real-world study confirms that aumolertinib demonstrates favorable efficacy as first-line treatment for EGFR-mutated locally advanced or metastatic NSCLC patients,aligning with findings from phase Ⅲ clinical trials.For patients in subgroup of baseline brain metastases,combining almonertinib with radiotherapy or bevacizumab is recommended to optimize outcomes.

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS)on the sleep disorder and examination results of recruits.Methods At a training base,the Pittsburgh Sleep Quality Index(PSQI)was used to screen the recruits with sleep disorders(total score of PSQI>7).The recruits were randomly assigned to rTMS group or sham rTMS group.Both groups received cognitive and behavioral intervention therapy,including sleep health education and relaxation training.Moreover,the rTMS group was treated with rTMS at the right posterior parietal lobe by continuous theta burst stimulation(cTBS)twice a day at an interval of at least 50 min for 5 consecutive days as a course of treatment with an interval of 2 days for a total of 2 courses of treatment.The coil position and stimulus intensity of sham rTMS group were consistent with the rTMS group,but the head of subjects was perpendicular to the coil plane and there was no effective stimulation.Before and after treatment,PSQI,self-rating depression scale,generalized anxiety disorder-7 and health questionnaire-15 were used to evaluate the sleep,mood and physical state of the recruits.The training result was assessed one month after treatment.The total effective rate of PSQI improvement and examination results were compared between the two groups.The independent influencing factors of excellent examination result were analyzed.Results Among 351 recruits,83 with sleep disorders completed treatment and follow-up.There were 40 patients in the rTMS group and 43 patients in the sham rTMS group.There was no significant difference between the two groups at baseline.After treatment,the total effective rate of PSQI improvement in the rTMS group was higher than that in the sham rTMS group(77.50%vs 53.49%,P=0.022).The average examination score and excellent rate of the rTMS group were higher than those of the sham rTMS group(91.58±3.19 vs 89.47±4.67,P=0.020;85%vs 65.12%,P=0.037).Logistic regression analysis showed that the treatment mode(rTMS group)was the independent influencing factor of excellent examination results(P=0.032).Conclusion rTMS can effectively and safely improve the sleep disorders and examination results of recruits.rTMS may play a positive role in improving the learning and training effect of recruits,which needs to be further proved.

Objective To investigate the protective effect and regulatory mechanism of ciprofol on Parkinson's disease(PD)rats based on the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α)signaling pathway.Methods Wistar rats were divided into blank control group,model group,ciprofol group,and ciprofol+AMPK inhibitor dorsomorphin group(ciprofol+Dor group),with 10 rats in each group.Except for the blank control group,PD models were estab-lished in the other three groups.Behavioral experiments were used to assess the motor and cognitive functions of rats in each group.Enzyme-linked immunosorbent assay(ELISA)was employed to de-tect the levels of dopamine(DA)and 5-hydroxytryptamine(5-HT)in the rat brain striatum.Immu-nofluorescence staining was conducted to measure the level of tyrosine hydroxylase(TH)in the rat brain substantia nigra.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was applied to detect the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,and Bax in the rat brain striatum.Western blot was used to determine the relative protein expression levels of ULK1,beclin1,Bcl-2,Bax,phosphorylated(p)-AMPK,SIRT1,PGC1α,and the ratio of LC3 Ⅱ to LC3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ)in the rat brain striatum.Results Compared with the blank control group,the motor and cognitive functions of rats in the model group were reduced,the levels of DA and 5-HT in the brain striatum decreased,the fluorescence intensity of TH in the brain substantia nigra weakened,and the relative mRNA expression levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were reduced.In contrast,the relative mRNA expression level of Bax and the relative protein expression level of Bax increased,with statistically significant differ-ences(P＜0.05).Compared with the model group,the motor and cognitive functions of rats in the ciprofol group were improved,the levels of DA and 5-HT in the brain striatum increased,the fluo-rescence intensity of TH in the brain substantia nigra strengthened,and the relative mRNA expres-sion levels of ULK1,beclin1,LC3,Bcl-2,as well as the relative protein expression levels of ULK1,beclin1,Bcl-2,p-AMPK,SIRT1,PGC1α,and LC3 Ⅱ/LC3 Ⅰ in the brain striatum were elevated.Meanwhile,the relative mRNA expression level of Bax and the relative protein expression level of Bax decreased,with statistically significant differences(P＜0.05).The comparison between the ciprofol+Dor group and the ciprofol group revealed that the AMPK inhibitor dorsomorphin could re-verse the effects of ciprofol(P＜0.05).Conclusion Ciprofol may exert neuroprotective effects for PD rats by promoting autophagy through activating the AMPK/SIRT1/PGC1α signaling pathway.

Objective To investigate the effects and related molecular mechanisms of esket-amine on the proliferation,epithelial-mesenchymal transition(EMT),and stem cell properties of colorectal cancer(CRC)cells.Methods CRC cell line SW480 was cultured with varying concentra-tions of esketamine,and the cells were divided into blank group(0 μmol/L),low-concentration group(1 μmol/L),medium-concentration group(5 μmol/L)and high-concentration group(10 μmol/L).Cell proliferation activity was assessed using the EdU proliferation assay,cell spheroid-forming ability was evaluated via the spheroid formation assay,cell migration capacity was measured using the scratch assay,cell invasion ability was determined through the transwell assay,and the expression levels of tumor stem cell property markers[NANOG homeobox(NANOG),SRY-box transcription fac-tor(SOX)2,SOX4],the neurogenic locus Notch homolog protein 1(Notch1)receptor and the Notch1 intracellular domain(Notch1 ICD)were detected by western blot.A recovery test was con-ducted by adding the Notch1 receptor agonist Jagged1 to the culture groups with different concentra-tions of esketamine.Results Compared with the blank group,esketamine significantly inhibited the proliferation activity,spheroid-forming ability,migration ability,and invasion ability of CRC cells in a concentration-dependent manner.The intracellular expression levels of SOX2,SOX4,NANOG,and Notch1 ICD proteins were significantly decreased,while the expression level of the Notch1 recep-tor was significantly increased in the esketamine groups(P＜0.05).After the addition of Jagged1,the inhibitory effects of esketamine on the proliferation activity,metastatic ability,and stem cell properties of CRC cells were alleviated.Conclusion Esketamine inhibits CRC cell proliferation,metastasis,EMT,and stem cell properties by reducing the activation level of the Notch1 receptor,demonstrating a potential for clinical anti-tumor applications.

The red doctor spirit， as an essential component of the Chinese Communist Party’s red health culture， is deeply rooted in the historical fertile soil of revolutionary practice. It serves as a crucial spiritual force driving the development of China’s healthcare undertakings and the reform of medical education. Anchored in firm political belief and a noble professional mission， it follows a dual path of constructing medical ethics and promoting humanistic care， thereby laying a solid cultural foundation for the modern medical education system in China. Integrating the spirit of red medicine into the ideological and political education system for medical students helps guide them in strengthening their ideals and beliefs， fulfilling their professional mission of healing the wounded and rescuing the dying， cultivating a rigorous and pragmatic work style， and establishing a professional spirit of pursuing excellence. Through the dual advancement of ideological guidance and practical instruction， the professional sense of responsibility among medical students can be further enhanced， providing sustained spiritual momentum for the cultivation of medical talents in the new era and the implementation of the “healthy China” strategy.

Objective: To design HBV DNA proficiency testing and system comparison samples with different concentration gradients, analyze their detection results in PCR detection systems, evaluate the nucleic acid detection capabilities of laboratories and differences between detection systems, and put forward suggestions for continuous quality improvement to participating laboratories. Methods: Three groups of randomly numbered proficiency testing samples (with HBV DNA reference concentrations of <2, 7.5, and 30 IU/mL respectively) were taken as the detection objects. Using nucleic acid test data from 11 provincial blood station laboratories as the source, the samples were grouped by detection system and laboratory successively, and statistical analysis was conducted. Results: Statistical analysis of the detection data of the three groups of samples based on detection systems and laboratories showed that from low to high concentration, the coincidence rate between the detection results of different detection systems and laboratories and the expected results showed an increasing trend: 38.89%, 85.90%, and 100.00%; the same system exhibited certain differences in performance among different laboratories. Conclusion: Through this proficiency testing and system comparison, it is found that there are certain differences in the detection capabilities of different laboratories and different nucleic acid test systems. Blood station laboratories should standardize processes, strengthen quality management and data analysis on the basis of being familiar with the detection performance of their detection systems, and at the same time strengthen the control of laboratory interference factors to continuously improve the nucleic acid detection capabilities of blood station laboratories.

Objective: To analyze the changing trend and distribution characteristics of hepatitis C virus (HCV) infection among blood donors in Hebei, thereby providing data to support strategy and procedure adjustment for blood collection and supply institutions. Methods: Data from 12 blood stations in Hebei Province from 2012 to 2021 were collected. These data were analyzed to determine trends in anti-HCV antibody double reagent reactive rate and to characterize its distribution among different donor categories, genders and birth cohorts. Results: During the period from 2012 to 2021, a total of 7.4576 million samples were tested at 12 blood stations in Hebei Province, with 3.4659 million (46.47%) from first-time donors, and 3.9917 million (53.53%) from repeat donors. The number (of anti-HCV double reagent reactive samples was 7167 (9.61/10 000). The anti-HCV double reagent reactive rate showed a annual downward trend (P<0.05), from 17.40/10 000 at the beginning to 4.95/10 000 at the end of the study period. Additionally, the double reagent reactive rate of repeat blood donors had remained below 1/10 000 since 2017. The double reagent reactive rate of first-time blood donors (19.42/10 000) was higher than in repeat donors (1.09/10 000) (P<0.05), and the double-reagent reactive rate of female first-time blood donors (20.98/10 000) was higher than that of male first-time blood donors (18.49/10 000) (P<0.05). The anti-HCV double reagent reactive rate among first-time donors exhibited two distinct peaks within the pre-1976 and 1989-1994 birth cohorts, with notable gender differences observed in both peak periods. The rate of double reagent reactive in females born before 1976 (52.22/10 000) was higher than that in males (32.28/10 000) (P<0.05), while that of males born in 1989-1994 was higher (25.75/10 000) than that of females (14.28/10 000) (P<0.05). Conclusion: The prevalenc of HCV infection among blood donors in Hebei Province has shown a consistent year-over-year decline over the study period. The majority of infected individuals are found among the first-time blood donors born before 1995. These trends and characteristics provide valuable insights for developing pre-blood collection screening strategies, analyzing nucleic acid test data in blood screening, adjusting blood screening procedures, and provide evidence for targeted screening of high-risk populations as part of public health initiatives to eliminate hepatitis C.

Objective To evaluate the efficacy of intravesical electrical stimulation (IVES) and low-intensity extracorporeal shock wave therapy (Li-ESWT) in improving bladder emptying function in female patients with non-obstructive detrusor underactivity (NODU), and to further assess the clinical value of an individualized integrated treatment strategy guided by reinforcement learning (RL) optimization. Methods A total of 98 female patients diagnosed with NODU by urodynamic testing at the Department of Urology, the Second People's Hospital of Hefei, duirng Jun.2023 and Feb.2025 were prospectively enrolled. Patients were randomly assigned (1∶1∶1) to three groups:the IVES group (n=33), the Li-ESWT group (n=35), and the RL group (n=30). Clinical outcomes before and after the 4-week treatment were compared among the three groups, including peak detrusor pressure during urination (PdetQmax), maximum urinary flow rate (Qmax), post-void residual (PVR), bladder contractility index (BCI), patient perception of bladder condition-scale (PPBC-S), incontinence impact questionnaire-short form 7 (IIQ-7), urogenital distress inventory-short form 6 (UDI-6), total efficiency and satisfaction.A RL model was trained based on clinical data, with a model structure diagram and reward convergence curve plotted to validate the utility of the RL system in optimizing individualized treatment parameters. Results There were no statistically significant differences in baseline characteristics among the three groups (P>0.05). After 4 weeks of treatment, all groups demonstrated significant improvements in PdetQmax, Qmax, and BCI, along with significant reductions in PVR, PPBC-S, IIQ-7, and UDI-6 scores (all P<0.01). Notably, the RL group exhibited significantly greater improvements in PdetQmax, Qmax, and BCI, and more pronounced reductions in PVR, PPBC-S, IIQ-7, and UDI-6 scores than the IVES and Li-ESWT groups (all P<0.05). Specifically, the RL group showed the most substantial improvements in Qmax, PVR, and BCI than the other two groups (all P<0.01). The total effective rate in the RL group was 90.0% (27/30), which was higher than that of the IVES group (81.8%,27/33) and the Li-ESWT group (77.1%,27/35), but the differences were not statistically significant (χ =2.63, P=0.27). The Li-ESWT group had a satisfaction rate of 51.4% (18/35), which was higher than that of the RL group (30.0%,9/30) and the IVES group (27.3%,9/33), but the differences were not statistically significant (χ =6.76, P=0.34). No serious adverse events were observed in any group. After approximately 200 iterations, the reward value of the RL agent stabilized, and the individualized treatment parameters recommended further optimized bladder emptying efficiency. Conclusion Compared to IVES and Li-ESWT, the RL-optimized individualized comprehensive treatment strategy can significantly improve the bladder emptying function in women with NODU.