Objective To study the differences in the blood cell analysis of male officers and soldiers be-tween in the high altitude area station and low altitude area station in summer.Methods A total of 239 male officers and soldiers in the high altitude area(Amdo Xizang,average altitude 4 800 m)and 336 male officers and soldiers in the low altitude area(Nanjing,Jiangsu,average altitude 30 m)from July 18 to 24,2022 were selected as the study subjects and the differences in blood cell analysis parameters of male officers and soldiers stationed between at high altitude and low altitude areas were retrospectively analyzed.Results The eosino-phils percentage(EDS％),eosinophils count(EOS)in the high altitude group were significantly lower than thosein the low altitude group(P＜0.05),and the basophillic granulocyte percentage(BASO％),basophillic granulo-cyte count(BASO)and monocyte percentage(MONO％)were significantly higher than those in the low alti-tude group,and the differences were statistically significant(P＜0.05),but which in the both groups were in the normal reference ranges.The red blood cell count(RBC)hemoglobin(Hb)and hematocrit(HCT)in the high altitude group were significantly higher than those in the low altitude group(P＜0.05),moreover Hb and HCT in the high altitude group were in the upper limit of the medical reference range.The mean corpus-cular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red blood cell distribution width-standard diviation(RDW-SD)in the high altitude group were lower than those in the low-altitude group(P＜0.05),but the both groups were in the normal reference ran-ges;there was no statistically significant difference in the erythrocyte distribution width coefficient of variation(RDW-CV)between the two groups(P＞0.05).The platelet(PLT)and thrombocytocrit(PCT)in the high altitude group were higher than those in the low altitude group,the platelet distribution width(PDW),mean platelet volume(MPV)and platelet large cell ratio(P-LCR)were lower than those in the low altitude group,and the differences were statistically significant(P＜0.05);PDW in the low-altitude group was at the upper limit of the medical reference range,and the other platelet-related indexes were in the normal range.Conclusion There are obvious differences in the blood cell analysis indicators of male officers and soldiers be-tween the high altitude area and low altitude area.

BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.

Objective:To investigate the changes in interaction proteome of NUS1 mutant R290C and their relations with pathogenicity of Lennox Gastaut syndrome (LGS). Methods:The wild-type and mutant NUS1(R290C) plasmids were constructed and transfected into human embryonic kidney HEK293T cells; 48 h after that, NUS1 protein expression in HEK293T cells was detected by Western blotting. Co-immunoprecipitation, silver nitrate staining, and proteomic analysis were used to analyze the proteins interacted with wild-type or mutant NUS1 and identify the differential interacting proteins. Enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to annotate the molecular function and signaling pathways involved in the differential proteins. DisGeNet database was used to analyze the association between differential proteins and human diseases. Protein-protein interaction (PPI) was used to analyze the interaction network of NUS1 with protein folding regulatory proteins (RTN4 and DHDDS) and developmental epileptic encephalopathy related proteins.Results:(1) There was no significant difference in NUS1 protein expression between the wild-type and mutant NUS1 transfected HEK293T cells ( t=0.536, P=0.620). (2) Compared with that with wild-type NUS1 plasmid, number of proteins interacting with mutant NUS1 plasmid was significantly reduced in the transfected cells; 310 differential interacting proteins were screened in the mutant NUS1. (3) GO and KEGG enrichment analyses showed that the differential proteins were mainly involved in protein folding reaction and translation regulation. (4) DisGeNet association analysis showed that the two most relevant proteins in the differential interacting proteins were associated with frontotemporal dementia and developmental epileptic encephalopathy. (5) PPI analysis showed that NUS1 may be involved in occurrence of neurological diseases such as LGS by affecting protein folding signaling pathways. Conclusion:NUS1 mutant R290C alters its interacting protein lineage and mediates the development of LGS and other neurological diseases probably by regulating protein folding-related signaling.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

BackgroundThe comorbidity rate of bipolar disorder and borderline personality disorder （BPD） is high， and the cognitive impairment of comorbidity patients is more serious. ObjectiveTo explore the difference of cognitive function between bipolar disorder patients with BPD or not， so as to provide references for clinical diagnosis and treatment. MethodsUsing simple random sampling， 60 patients with bipolar disorder comorbidity BPD treated in the First Hospital of Hebei Medical University from April 2021 to April 2022 were selected as the research group， including 33 patients with bipolar depression and 27 patients with bipolar mania. At the same time， 60 patients with bipolar disorder were randomly selected as the control group， including 35 patients with bipolar depression and 25 patients with bipolar mania. The cognitive function of patients was evaluated by the Chinese version of Repeatable Battery for the Assessment of Neuropsychological Status （RBANS） and the Stroop Color Word Test. ResultsThe immediate memory， visual span， speech function and total score of RBANS in the comorbid group were lower than those in the non-comorbid group， and the differences were statistically significant （t=-2.356， -2.138， -3.306， -2.729， P<0.05 or 0.01）. The single word time， single color time， double word time and double color time in Stroop Color Word Test in comorbid group were longer than those in non-comorbid group， and the differences were statistically significant （t=4.808， 3.341， 5.249， 5.167， P<0.01）. The immediate memory， visual span， speech function and total score in RBANS of bipolar depression patients with comorbid BPD were lower than those of bipolar depression patients without comorbid BPD （t=-2.446， -2.407， -2.231， -2.078， P<0.05）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those of non-comorbid BPD patients （t=-3.652， 3.035， 4.406， 5.016， P<0.01）. The speech function and total score of RBANS in bipolar manic patients in comorbid group were higher than those in non-comorbid group （t=-2.777， -2.347， P<0.05 or 0.01）， and the time of single word， single color， double word and double color in Stroop Color Word Test were longer than those in non-comorbid group （t=3.600， 2.658， 2.943， 4.337， P<0.05 or 0.01）. ConclusionThe cognitive impairment of bipolar disorder patients comorbid with BPD is more severe than that of patients without comorbid with BPD. ［Funded by Medical Science Research Project of Hebei Province in 2022 （number， 20221407）］

Rotator cuff injury often leads to shoulder pain and dysfunction. For the injured rotator cuff tendon without continuous interruption, conservative treatment is often used. However, the shoulder is used frequent in daily life, which makes that the rotator cuff injury generally shows gradual aggravation and eventually progresses to complete tear due to poor blood supply of the rotator cuff tendon tissue and weak repair ability. In order to reverse the pathophysiological changes after rotator cuff injury and promote the repair of injured rotator cuff tendon, a series of conservative treatments for rotator cuff injury have been explored. Extracorporeal shock wave therapy (ESWT) is one of the representative treatments, but its molecular biological mechanism in promoting rotator cuff repair is still unclear. Therefore, the authors review the progress of ESWT for rotator cuff injury from aspects of the molecular biological mechanism and clinical application status, so as to provide a reference for future researches and clinical application of ESWT.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Objective To explore the correlation between childhood trauma and plasma adiponectin levels in patients with depression.Methods A total of 121 patients with depression and 39 healthy controls(control group)were enrolled.Childhood trauma questionnaire(CTQ-SF)was used to assess the experience of childhood abuse and neglect,and the patients with depression were divided into trauma group(n=53)and non-trauma group(n=68)according to the CTQ-SF score.The 17-item Hamilton depression scale-17(HAMD17)and the Hamilton anxiety scale(HAMA)were used to evaluate the severity of depression and anxiety symptoms,respectively.Plasma adiponectin levels of subjects were measured by enzyme-linked immunosorbent assay.Results The plasma adiponectin level of trauma group[3.82(2.44,4.92)μg/mL]was significantly lower than that of non-trauma group[4.64(2.98,6.43)μg/mL,P=0.01]and the control group[6.29(4.54,7.51)μg/mL,P＜0.01].The plasma adiponectin level of non-trauma group was lower than that of the control group(P＜0.01).Correlation analysis showed that plasma adiponectin level in patients with depression was negatively correlated with childhood trauma(r=-0.34,P＜0.01).Multivariate linear regression analysis showed that plasma adiponectin level was negatively correlated with childhood trauma scores in patients with depression(β=-0.05,P＜0.01).Conclusions Patients with depression who have experienced childhood trauma have lower plasma levels of adiponectin,and childhood trauma may be associated with decreased plasma adiponectin levels in patients with depression.

This article summarizes the pregnant women's readiness for discharge from five aspects, including the concept, research status at home and abroad, evaluation tools, influencing factors, and interventions of readiness for discharge, so as to provide reference for future research on pregnant women's readiness for discharge.

Objective:To explore the diagnostic value of ultrasound in posterior fossa anomalies (PFA) at 11-13 + 6 gestational weeks by measuring brainstem (BS), brainstem-to-occipital bone (BSOB) diameter and BS/BSOB ratio. Methods:A total of 209 normal fetuses (control group) were randomly selected from Beijing Obstetrics and Gynecology Hospital, Capital Medical University, between March 2018 and November 2021. Reference ranges for BS, BSOB diameter and BS/BSOB ratio were obtained on the mid-sagittal view of the fetal profile and the relationship of three parameters and crown-rump length (CRL) was investigated. The intra- and inter-observer reliabilities were determined by intraclass correlation coefficient (ICC) in 30 normal fetuses. Fourteen fetuses diagnosed with PFA in the same period including 10 cases of cystic posterior fossa malformations (cPFM) and 4 cases of open spine bifida (OSB) were retrospectively selected to compare BS, BSOB diameter and the BS/BSOB ratio with control group.Results:BS and BSOB diameters were successfully obtained in all control fetuses (100%), and the intra- and inter-observer reliabilities for BS and BSOB diameters were good (ICC=0.877, 0.846 and 0.939, 0.895). In the control group, BS and BSOB diameter linearly correlated with CRL ( r=0.867, 0.794; all P<0.001), while the BS/BSOB ratio was 0.75 (0.71, 0.79). There were significant differences of BSOB diameter and BS/BSOB ratio between control group and PFA group (all P<0.05). Except for one isolated vermian hypoplasia (VH), the BSOB diameters in 9 (90%) cases of cPFM were above the 95th percentile of the calculated normal range and were below the 5th percentile in 4(100%) cases of OSB.Except for one isolated VH, the BS/BSOB ratio in 9 (90%) cases of cPFM was below the 5th percentile of the calculated normal range. The BS/BSOB ratio in 4 (100%) cases of OSB was above the 95th percentile of the calculated normal range. Conclusions:The measurements of BS and BSOB diameter are feasible with good repeatability. Abnormal BSOB diameter and BS/BSOB ratio are suggestive for PFA. The posterior fossa of isolated VH can be normal in the first trimester.