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 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.

Objective: To explore the association between single nucleotide polymorphism(SNP) in the arachidonate 15-lipoxygenase(ALOX15) gene and Helicobacter pylori(H. pylori) infection as well as the risk of non-cardia gastric cancer in Baotou Han population, and to provide experimental evidence and data support for the screening of susceptible population for non-cardia gastric cancer. Methods: A total of 458 cases with non-cardia gastric cancer and 460 healthy examination people were collected. The 14C urea breath test(UBT) and enzyme-linked immunosorbent assay(ELISA) were used to detect H. pylori infection in the 460 healthy individuals. The genotypes of ALOX15 rs2619112, rs2619118, rs2664593, rs7220870 were detected by polymerase chain reaction-restriction fragment length polymorphism, and the association of SNP with H. pylori infection as well as the risk of non-cardia gastric cancer was statistically analyzed. Results: The positive rate of H. pylori infection was 42.4%. ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 had no association with H. pylori infection. ALOX15 rs2619112, rs2664593, and rs7220870 were not associated with the risk of non-cardia gastric cancer. Compared with the carriers of(CC + CT) genotype, the carriers of rs2619118 TT genotype had an increased onset risk of non-cardia gastric cancer [OR(95%CI)=1.512(1.110-2.060)]. The haplotype ACCC constructed by ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 could reduce the onset risk of non-cardia gastric cancer. The second-order interaction of ALOX15 rs2619112 and rs2619118 was associated with the risk of non-cardia gastric cancer ( P < 0. 05 ) . Conclusion ALOX15 rs2619112 , rs2619118 , rs2664593 , rs7220870 may not play a major role in H. pylori infection. ALOX15 rs2619118 TT genotype is a risk factor for the development of non⁃cardia gastric cancer. The haplotype ACCC constructed by ALOX15 rs2619112 , rs2619118 , rs2664593 , and rs7220870 reduces the onset risk of non⁃cardia gastric cancer. The interaction of ALOX15 rs2619112 and rs2619118 has a synergistic effect in the development of non⁃cardia gastric cancer.

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 investigate the distribution and drug resistance of pathogens isolated from the elderly population with infections in Baotou,Inner Mongolia.METHODS The clinical data were collected from 9268 elder-ly patients with infections(with no less than 60 years of age)who were treated in Baotou Medical College of Cen-ter Clinical Medical School and the Second Affiliated Hospital of Baotou Medical College from 2017 to 2021 and were retrospectively analyzed.The 9268 samples were cultured for isolation of pathogens,the isolated pathogens were identified,and the drug susceptibility testing was performed.RESULTS Totally 9268 strains of pathogens were isolated,53.11％of which were gram-negative bacteria,28.94％were gram-positive bacteria,and 17.95％were fungi.Escherichia coli and Klebsiella pneumoniae were the major species of gram-negative bacteria;Entero-cocci and coagulase-negative Staphylococcus were dominant among the gram-positive bacteria;Candida albicans was the predominant species of fungi.There were certain differences in the pathogens isolated from the elderly pa-tients with infection between different sexes,among the different seasons and age groups.With respect to drug re-sistance,the gram-positive bacteria maintained highly sensitive to vancomycin and teicoplanin,while the drug re-sistance rates to ampicillin and penicillin were relatively high.The drug resistance rates of the gram-negative bacte-ria to carbapenems were relatively low,but the drug resistance rates to ampicillin and cefazolin were high.CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the elderly population with infections in Baotou City,Inner Mongolia;the distribution of pathogens is affected by the sex,age and sea-son.There is serious problem with the drug resistance of pathogens,the strains are highly resistant to the com-monly used antibiotics such as ampicillin and penicillin.It is necessary for the hospital to reasonably use antibiotics according to the epidemiological characteristics and drug resistance trends of the pathogens and optimize the strate-gies for clinical diagnosis and treatment of infectious diseases.

Objective:To compare the efficacy of lateral placement of the intramedullary nail guide pin versus that of median placement of the intramedullary nail guide pin in the closed reduction of metaphyseal fracture of the distal tibia.Methods:A retrospective cohort study was conducted to analyze the clinical data of 48 patients with metaphyseal fracture of the distal tibia who had been admitted to Department of Trauma Orthopaedics, The Second General Hospital of Fuzhou from May 2019 to July 2023. There were 37 males and 11 females, aged (46.0±12.4) years. According to the AO classification, 37 patients were classified as type A1, and 11 ones as type A2. The patients were divided into 2 groups according to the distal positioning of the intramedullary nail guide pins during operation. In the lateral placement group of 26 patients, the distal positioning of the guide pins was located at 1/3 lateral to the articular surface of the distal tibia. In the median placement group of 22 patients, the distal positioning of the guide pins was located at the midpoint of the articular surface of the distal tibia. The operation time, intraoperative blood loss, hospital stay, fracture healing time and fracture reduction were recorded and compared between the 2 groups. Moreover, the visual analogue scale (VAS) pain score, American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, and range of motion of the affected ankle were compared between the 2 groups, as well as within the 2 groups. The complications were compared between the 2 groups at the last follow-up.Results:There were no significant differences in the demographic data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.6±4.4) months. The operation time [(81.7±17.3) min], intraoperative blood loss [(78.4±12.2) mL], hospital stay [(5.7±2.1) d] and fracture healing time [(4.3±1.1) months] in the lateral placement group were significantly less than those in the median placement group [(103.0±13.4) min, (111.4±11.7) ml, (8.6±3.5) d, and (6.1±1.3) months] ( P<0.05). There was no significant difference in the VAS pain score between the 2 groups before operation or at the last follow-up ( P>0.05). At the last follow-up, the AOFAS ankle-hindfoot score [(93.6±1.6) points], ankle dorsiflexion (17.9°±1.6°) and plantar flexion (41.9°±1.9°) in the lateral placement group were significantly better than those in the median placement group [(87.8±3.2) points, 15.1°±1.2°, and 38.5°±2.7°] ( P<0.05). In both groups, significant improvements were achieved at the last follow-up in VAS pain score, the AOFAS ankle-hindfoot score, ankle dorsiflexion and plantar flexion compared with the preoperative period ( P<0.05). The incidence of fracture angulation deformity in the lateral placement group (11.5%, 3/26) was lower than that in the median placement group (31.8%, 7/22) ( P>0.05). There was no significant difference in the incidence of complications between the lateral placement group (3.8%, 1/26) and the central placement group (18.2%, 4/22) ( P>0.05). Conclusion:In the closed reduction of metaphyseal fracture of the distal tibia, compared with median placement of the intramedullary nail guide pin, lateral placement of the intramedullary nail guide pin assisted with a Kirschner wire demonstrates advantages of more rapid and effective closed reduction of the fracture, shortened operation time, reduced intraoperative blood loss and promoted postoperative rehabilitation.

Objective:To compare postoperative inflammatory markers and surgical outcomes between open reduction and internal fixation versus double reverse traction closed reduction and percutaneous internal fixation for tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 229 patients with tibial plateau fracture who had been admitted to Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University from January 2023 to December 2023. There were 155 males and 74 females with an age of (48.7±10.9) years. According to the surgical methods, the patients were divided into 2 groups. A conventional group of 87 cases were treated by open reduction and internal fixation while a minimally invasive group of 142 cases treated with double reverse traction closed reduction and percutaneous internal fixation. The 2 groups were compared in terms of hematological indexes [white blood cell count (WBC), neutrophil count (NEUT), lymphocyte count (LYM), monocyte count (Mono), platelet count (PLT), and albumin (ALB)] and composite inflammatory indexes [neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI)] before operation and on the first day after operation, intraoperative blood loss, operation time, fracture healing time, Hospital for Special Surgery (HSS) knee score and incidence of thrombosis.Results:There were no significant differences in baseline characteristics or treatment variables between the 2 groups, indicating comparability ( P > 0.05). All the 229 patients were followed up for (16.5±2.8) months. In each group, comparisons between preoperation and postoperation showed that LYM and ALB significantly decreased while WBC, NEUT, Mono, PLT, NLR, PLR, SII and SIRI significantly increased on the first day after operation ( P < 0.05). Preoperatively, there were no significant differences between the 2 groups in terms of hematological or composite inflammatory indexes ( P > 0.05). On the first day after operation, there was no significant difference in WBC, NEUT, LYM, ALB or NLR between the 2 groups ( P > 0.05), but Mono, PLT, PLR, SII and SIRI in the minimally invasive group were significantly lower than those in the conventional group ( P < 0.05). The intraoperative blood loss, operation time, fracture healing time, HSS knee score and incidence of thrombosis in the minimally invasive group were significantly better than those in the conventional group ( P < 0.05). Conclusion:In the treatment of tibial plateau fractures, compared with conventional open reduction and internal fixation, double reverse traction closed reduction and percutaneous internal fixation shows obvious advantages in reducing inflammatory indicators and leads to better surgical outcomes.