Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
Mice ; Animals ; Depression/etiology* ; Antidepressive Agents/pharmacology* ; Brain-Derived Neurotrophic Factor ; Serotonin

Objective: To investigate the clinicopathological features and differential diagnoses of paratesticular liposarcoma. Methods: The cases were collected from 2012-2020, from the archives of the Department of Pathology, Peking University Third Hospital, with diagnosis confirmed by histology, immunostaining and FISH tests. Results: Totally 19 patients were enrolled (including 11 in-hospital patients and 8 consultant cases). The patients aged 37-84 years (mean 57 years). The preoperative clinical diagnoses were spermatic cord/inguinal masses (nine patients), scrotal masses (seven patients), and inguinal hernia (three patients). Six lesions recurred after local resection, including one case extending from pelvic liposarcoma. Histologically, there were 10 cases of well-differentiated liposarcoma (WDLPS) and nine cases of dedifferentiated liposarcoma (DDLPS). WDLPSs mostly showed the combined features of lipoma-like, inflammatory and sclerosing subtypes (six patients); the other four WDLPSs had pure lipoma-like subtype features. DDLPSs were low-grade (three patients) or high-grade (six patients), with the morphology resembling myxofibrosarcoma, inflammatory myofibroblastoma, spindle cell sarcoma, pleomorphic undifferentiated sarcoma and pleomorphic liposarcoma. Intense inflammatory cells infiltration was commonly observed in five WDLPSs and two DDLPSs. Ossification was observed in three tumors. Immunohistochemically, the tumors were positive for MDM2 (8/10) and CDK4 (10/10), which were expressed in lipo-differentiating cells, spindle cells in WDLPS, and in dediffferentiated components. S-100 was only expressed by lipocytes (10/10). CD34 expression was positive and diffuse in the stromal cells of WDLPSs and focal or diffuse in dedifferentiated areas (10/10). FISH tests with an MDM2 gene probe were positive (12/12). Conclusions: Paratesticular liposarcoma may be overlooked by both clinicians and pathologists. WDLPS and DDLPS predominate, showing various histologic divergences. The presence of amplification of the 12q14-q15 region (containing the MDM2 and CDK4 genes) is helpful for making the correct diagnosis.
Adult ; Genital Neoplasms, Male/surgery* ; Humans ; In Situ Hybridization, Fluorescence ; Liposarcoma/surgery* ; Male ; Proto-Oncogene Proteins c-mdm2/genetics* ; Soft Tissue Neoplasms

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.
Child ; China ; Consensus ; Cross-Sectional Studies ; Humans ; Off-Label Use ; Pharmaceutical Preparations

OBJECTIVE: To investigate the molecular mechanism of one patient with abnormal serological phenotype in RhD and discuss the transfusion strategy. METHODS: The RhD variant sample was screened from a patient with IgM type anti-D antibody and further determined by three different sources of anti-D antibodies. Ten exons and the adjacent introns of the RHD gene were amplified, purified and sequenced. RhCE phenotypes and RHCE genotypes were detected. RESULTS: The patient with Rh variant showed abnormal results of serological tests. The RHD gene sequence analysis showed that the RHD*01W.01 with a variation (c.809T>G, p.Val270Gly) in exon 6 of the RHD gene was found in the patient. The RhCE phenotype was CcEe. The genotyping results of RHCE were consistent with the serological typing results. CONCLUSION The Rh variant of the patient is RHD*01W.01, these findings indicate that RhD variants should be analyzed by molecular assays for the sake of safe transfusion.
Alleles ; Blood Transfusion ; Exons ; Genotype ; Humans ; Phenotype ; Rh-Hr Blood-Group System/genetics*

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.
Cancer Vaccines/therapeutic use* ; Cervical Intraepithelial Neoplasia/prevention & control* ; Female ; Humans ; Papillomavirus Infections/prevention & control* ; Papillomavirus Vaccines/therapeutic use* ; Precancerous Conditions/therapy* ; Uterine Cervical Neoplasms/prevention & control*

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation ( CONCLUSIONS A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.
Birth Weight ; Bone Diseases, Metabolic/etiology* ; China/epidemiology* ; Female ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies ; Risk Factors

OBJECTIVE: To investigate the indentification method of samples mistyped as O phenotype and to explore the precision transfusion strategy. METHODS: The blood samples from donors and patients admitted in our center from 2018 to 2019 was collected. The samples with O phenotype suspected subtypes were further determined by tube test, adsorption-elution test, etc. Molecular testing was used to sequence the related blood type genes of the subjects. RESULTS: Among 14 subjects misjudged as O, 11 different genotypes were identified, in which 3 blood donors were Ael02/O02, Bel03/O02, and one para-Bombay with B101/O02 (FUT1: h3h3; FUT2: Se CONCLUSION The phenotypes of Ael, Bel, Aw and para-Bombay subtypes are easily misjudged as type O. Molecular technology is helpful to identify the genotype of subtypes, and the corresponding transfusion strategies could be reasonably performed.
ABO Blood-Group System ; Alleles ; Blood Transfusion ; Fucosyltransferases/genetics* ; Genotype ; Humans ; Phenotype

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

As a new type of cell death, necroptosis is initiated by tumor necrosis factor receptor 1(TNFR1), and then activated receptor-interacting protein kinase 1(RIP1) and receptor-interacting protein kinase 3 (RIP3), following by the activation of mixed lineage kinase domain-like protein(MLKL) to deliver cell death signal. When necroptosis happens, damage associated molecular patterns (DAMPs) enter into extracellular area through the ruptured cytomembrane, followed by the disordered tissue hemeostasis. In recent years, many researches showed that necroptosis playimportant roles in a few bone related diseases, such as osteoporosis, osteonecrosis, osteosarcoma, etc. Thus, we try to briefly review the researches in this field.
Apoptosis ; Necroptosis ; Protein Kinases