Chemotherapy is an important treatment for tumors， but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine （TCM） has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors， such as cold-natured （e.g. Scutellaria baicalensis， Rhus chinensis）， cool-natured （e.g. Ligustrum lucidum， Ophiopogon japonicus）， warm-natured （e.g. Panax ginseng， Epimedium brevicornu， Curcuma longa， Angelica sinensis）， hot-natured （e.g. Cinnamomum cassia， Aconitum carmichaeli）， and neutral-natured （e. g. donkey-hide gelatin， Lycium barbarum， Rhodiola rosea， fungi）， can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells， improving the bone marrow hematopoietic microenvironment， inhibiting the oxidative stress response， regulating signaling pathways， so as to ultimately repaire inflammatory damage and improve hematopoietic function， thereby playing an anti-myelosuppressive role.

Attenuated psychosis syndrome(APS)is a clinical disorder associated with a high risk of psychosis.Patients during this period typically exhibit multidimensional neurocognitive and social cognitive impairment.Cognitive impairment in APS patients is associated with structural and functional abnormalities in the frontal,temporal and subcortical brain regions.At present,drug therapy,psychotherapy,nutritional therapy and computer cognitive training are mainly used to improve the cognitive function of APS patients.In the future,we could comprehensively utilize brain imaging,electrophysiology,and molecular imaging to deeply explore the neuropathological mechanism of APS cognitive impairment,and combine computer,virtual reality,and artificial intelligence to develop new cognitive function intervention procedures,in order to achieve APS precise prevention and treatment.

Objective To investigate the design of cuffed pediatric tracheal tubes and compare the effects of different tracheal intubation depth placement strategies on the position of the tracheal tube tip and cuff of 5 tracheal tube brands.Methods A total of 180 children who were admitted to Tianjin Children's Hospital from October 2020 to December 2021,with endotracheal intubation under general anesthesia,aged 1-6 years,were enrolled.The length of the subglottic airway was measured by electronic bronchoscopy.Dimensional data from 5 cuffed pediatric tracheal tube brands were recorded,including the length of the tracheal tube cuff,the distance from the tip of the tracheal tube to the upper edge of the cuff,and the tip of the tracheal tube to the lower edge of the tube glottis marker line the distance.Calculation of the required cuffed endotracheal tube internal diameter(ID)for 180 pediatric patients was performed based on the Motoyama formula,the positions of tracheal tube tip and upper cuff border were calculated for each of the 180 tracheas using depth mark to based tracheal tube placement,placement of the tracheal tube tip at 2 cm above the carina,and mid-tracheal tube placement.Results There were differences in the dimensional data of the 5 cuffed pediatric tracheal tube brands.Depth mark-based tracheal tube placement resulted in the incidence rate of tube tip to carina placement less than 1 cm was 3.9%-67.8%,and the highest incidence of bronchial intubation is Ruijing,up to 17.8%.The tracheal tube tip was placed 2 cm above the carina,and no improper placement of the tracheal tube cuff and tube tip was found in all brands.Mid-tracheal tube placement led to 100%subglottic and supraglottic tracheal tube cuff positions,except Weili.Conclusions There are differences in design between different brands of cuffed pediatric tracheal tube,and some of the design deficiencies may lead to the risk of airway complications.The method used to guide the insertion depth and the brand of cuffed tracheal tubes can affect the tracheal tube position.Placement of the tracheal tube tip at 2 cm above the carina allowed safe tracheal tube placement in children aged 1-6 years.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective To analyze the sequence of LysinB protein in bacteriophage TM4,express LysinB protein in E.coli and evaluate its bactericidal activity in vitro.Methods Bacteriophage TM4 LysinB gene was synthesized and the recombinant prokaryotic expression plasmid was constructed.The soluble protein was induced and purified.The biological characteristics of bacteriophage TM4 LysinB protein were analyzed by online software program.Mycobacterium smegmatis was cultured in 7H9 medium,and its bactericidal effect and stability were detected.Results The theoretical isoelectric point was 6.66,the instability index was 28.71,which was a stable and amphiphilic protein.In the secondary structure,The random coil,α-helix,β-fold and turn Angle accounted for 42.00％,40.25％,12.00％and 5.75％;In the tertiary structure,the content of random coil was high.The peptide composed of AA at positions 11 to 73 constituted the peptidoglycan binding domain.The regions of B cell epitopes and the strong binding peptides of T cell epitopes were predicted.LysinB protein has a significant ability to kill Mycobacterium smegmatis in vitro.PBST protein buffer with pH8.0 was beneficial to maintain the bactericidal effect of LysinB proteins during the experimental cycle.Conclusion This study expands the comprehensive understanding of the LysinB protein of mycobacterial phage TM4 lyase,and also provides reference for the development of stable storage of phage enzyme preparation and its clinical application.

Objective:To explore the differences in therapeutic effect and prognosis of different molecular subtypes of breast invasive lobular carcinoma treated with nab-paclitaxel, so as to provide a basis for the selection of clinical drugs for breast cancer.Methods:The data of 180 patients with advanced invasive lobular carcinoma of the breast who were treated in Handan Central Hospital and the Fourth Hospital of Hebei Medical University from January 2017 to January 2020 were retrospectively analyzed, including 34 cases of Luminal A type, 92 cases of Luminal B type, 21 cases of human epidermal growth factor receptor 2 (HER2) overexpression type, and 33 cases of triple-negative type. The patients were treated with nab-paclitaxel, and the clinical curative effect was evaluated according to the solid tumor response evaluation criteria version 1.1 after 1 year of treatment, and the objective response rate (ORR) (calculated as complete remission + partial remission) and clinical benefit rate (CBR) (calculated as complete remission + partial remission + stable disease) were calculated; the occurrence of adverse reactions during the treatment was recorded. The Kaplan-Meier method was used to draw the progression-free survival (PFS) and overall survival (OS) curves for each subtype of patients, and the log-rank method was used to test them.Results:The differences in ORR and CBR among patients with the four subtypes of Luminal A, Luminal B, HER2 overexpression, and triple-negative were statistically significant (all P < 0.001), with the triple-negative type having the lowest ORR and CBR [21.2% (7/33) and 63.6% (21/33)] and the Luminal A type having the highest ORR and CBR [70.6% (24/34) and 100.0% (34/34)]. The ORR and CBR of Luminal B type were 45.7% (42/92) and 90.2% (83/92), and the HER2 overexpression type was 38.1% (8/21) and 90.5% (19/21). The differences in the incidence of myelosuppression, numbness of limbs, joint and muscle pain among the four subtypes were statistically significant (all P < 0.05), with the triple-negative type having the highest incidence of all of the above adverse reactions. The PFS and OS of triple-negative subtype were worse than those of Luminal A, Luminal B and HER2 overexpression subtypes, and the differences were statistically significant (all P < 0.05). Conclusions:The clinical response and prognosis of patients with different molecular subtypes of invasive lobular carcinoma is significantly different after nab-paclitaxel intervention, among which the prognosis of patients with triple-negative type is the worst, and the clinical medication can be guided according to the pathological test results.

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development

Objective:To investigate the flow cytometric characteristics of bone marrow in patients with aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypoMDS) and its value in differential diagnosis between AA and hypoMDS.Methods:A total of 618 patients were recruited from Shandong Provincial Hospital affiliated to Shandong First Medical University from January 2017 to December 2021, including 441 patients as controls with abnormal peripheral blood counts but confirmed to have no AA, hypoproliferative MDS, or other hematological tumors, 57 patients with AA, 52 patients with hypoMDS and 68 patients with diluted bone marrow. The proportions of bone marrow myeloid progenitor cell, lymphocyte, neutrophil and erythroid cell in bone marrow were analyzed by flow cytometry immunophenotyping. The differences between the four groups were compared by Kruskal-Wallis one-way ANOVA. The diagnostic efficacy was evaluated by the receiver operating characteristic (ROC) curve.Results:The proportion of myeloid progenitor cells in control group was [0.30%(0.20%, 0.46%)]; the proportion of myeloid progenitor cells in AA group was [0.00 (0.00, 0.04)]%, while the proportion of myeloid progenitor cells in hypoMDS group was [3.10%(1.25%, 6.71%)]. The proportion of myeloid progenitor cells in AA group was lower than that in control group( χ2=302.90, P<0.001), while the proportion of myeloid progenitor cells in the bone marrow of patients with hypoMDS was higher than that in the control group ( χ2=203.88, P<0.001). The area under the ROC curve for identifying AA and hypoMDS by the ratio of myeloid progenitor cells in bone marrow is 0.996, with the sensitivity of 96.2% and the specificity of 100% when the cutoff value is 0.21%. The proportion of bone marrow lymphocytes in control group was [10.39%(7.33%, 14.80%)]; the proportion of bone marrow lymphocytes in AA group was [52.67%(42.20%, 67.68%)], and the proportion of bone marrow lymphocytes in hypoMDS group was [24.68%(15.51%, 35.19%)]. The proportion of bone marrow lymphocytes in AA group or hypoMDS group was higher than that in control group( χ2=298.74, P<0.001; χ2=194.33; P<0.001), and the proportion of bone marrow lymphocytes in AA group is higher than that in hypoMDS group, with a statistically significant difference( χ2=104.41, P=0.002). The area under the ROC curve for identifying AA and hypoMDS by the ratio of bone marrow lymphocyte is 0.882, with the sensitivity of 78.9% and the specificity of 92.3% when the cutoff value is 41.6%. Conculsion:Patients with AA and hypoMDS could be differentiated effectively by the proportions of myeloid progenitor cell and lymphocyte in bone marrow by flow cytometry immunophenotyping.

【Objective】 To investigate the gene frequency and polymorphism of RBC blood group systems in RhD negtive population in Hunan, so as to lay a foundation for clinical blood transfusion and construction of multiple rare blood group database. 【Methods】 Blood samples were taken from 300 RhD negative blood donors, confirmed by serological method, from June 2019 to June 2020,. RHD genotyping was performed by SSP-PCR. For blood donors with typing results as RhD negative plus RHD gene deletion, antigens genotyping of MNS, Duffy, Kell, Domrock, Diego, Kidd, Sciawnna, Colton, Lutheran and Yt RBC blood group systems were performed by SSP-PCR and analyzed by the chi square test of SPSS 20 statistical software. 【Results】 RHD gene deletions accounted for 58.67% (176 / 300) of serological D negative blood donors. The gene frequencies were as follows: MNS: GYPB^*S=0.045 5(8/176), GYPB^*s=0.954 5(168/176), GYP^*Dane=0.039 8(7/176); Duffy: FY^*A =0.965 6(170/176), FY^*B=0.034 1(6/176); Dombrock: DO^*A=0.082 4(14.5/176), DO^*B=0.917 6(161.5/176); Diego: DI^*A=0.025 6(4.5/176), DI^*B =0.974 4(171.5/176); Kidd: JK^*A=0.485 8(85.5/176), JK^*B=0.514 2(90.5/176); Kell: KP^*A=0.005 7(1/176), KP^*B=0.994 3(175/176); Lutheran: LU^*A=0.005 7(1/176), LU^*B=0.994 3(175/176); Yt: YT^*A=0.002 8(0.5/176), YT^*B=0.997 2(175.5/176). The genotypes of Kell(K+ /k+ ), Scianna and Colton blood groups were KEL^*02 /KEL^*02, SC^*01 /SC^*01 and CO^*A /CO^*B, respectively. The expected frequencies of the combination of type O, RhD negative and other blood group systems were between 1/100 000 to 1/10 000. 【Conclusion】 Among RhD negative blood donors in Hunan, the gene profiles of MNS, Duffy, Domrock, Diego, Kidd, Kell and Lutheran blood group system were polymorphic, and Kell (K+ /k+ ), Colton and Scianna were homozygous. The data of other RBC blood group systems from RhD negative blood donors is of great significance to establish local database of rare blood groups.

Objective:To improve the rate of successful rescue through analyzing the clinical features and treating processes of septic shock caused by lymphocyst infection after lymph node dissection in diabetic patients.Methods:A total of 462 cases of diabetic patients with bladder, prostate, renal cancers, cervical, endometrial and ovarian were retrospectively analyzed, all of whom underwent standard surgical treatments including pelvic lymph node dissection, hospitalized in department of urology surgery and gynecology of Sun Yat-sen Memorial Hospital from Jan 2015 to Jan 2020. Lymphocytes were confirmed in 148 cases, of which 89 cases were complicated by infection, and 13 cases developed septic shock. Patients with lymphocyst infection were divided into shock and non-shock groups, and age, sex, duration of diabetes, BMI, glycosylated hemoglobin at admission, number of lymph nodes surgically removed, retention time of drainage tube after operation, maximum diameter of lymphocyst and time between infection and previous chemotherapy were compared. The initial symptoms, blood routine in the first time after the onset of the infection, the time from onset to drainage puncture and catheterization and the final outcomes were analyzed in 13 patients with septic shock. The results of pathogen culture and drug sensitivity of infected lymphocyst fluid were also analyzed.Results:Categorical variable test showed that: in diabetic patients with lymphocyst infection, there were significant differences in glycosylated hemoglobin ( P=0.018) , adjuvant chemotherapy ( P=0.014) and lymphocyst size ( P<0.001) between shock group and non-shock group. Among the 13 cases of septic shock, 11 caseshad mild to moderate fever or abdominal pain. The total leukocyte count of all cases in the first hemogram were less than 20×10 9/L. The average time from onset to drainage was 33 hours. Among the 13 patients, 5 developed MODS and 1 died. There were 2 patients whose conditions were complex with frequent fluctuations. In the 12 patients who recovered from septic shock, only 1 underwent a residual lymphocyst pretreatment, 4 had recurrent cyst infection for 1-2 times, 2 had septic shock again, and 1 died. Gram negative bacteria were the most common pathogens, and the main was Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Piperacillin / tazobactam, carbapenems and tigecycline were commonly sensitive, while the drug resistance rates of ceftazidime, ceftriaxone and levofloxacin were more than 50%. Conclusions:Poor glycemic control, adjuvant chemotherapy and big lymphocyst size(d≥5 cm) are the high risk factors of septic shock. Most of shock patients' initial symptoms and total white blood cell count have no warning significance, leading to longer time from infection to drainage, and delayed treatment. Early diagnosis, timely drainage and active anti-infection treatment are the key to a successful treatment. The possibility of connection between lymphocyst and surrounding organ should be considered when the treatment effect is not good. After septic shock of postoperative lymphocyst infection in patients with diabetes, the larger esidual lymphocyst should be intervened actively to avoid serious infection again.