Objective:To preparation TREM2-specific monoclonal antibodies and to evaluation their properties and applica-tions lay a foundation for the development of druggable antibodies against TREM2 targets.Methods:The GST fusion protein containing the extracellular segment of TREM2 was expressed and purified,which was used as antigen to immunize mice.The mouse with high antiserum titer was used to generate specific monoclonal antibodies against TREM2 through cell fusion and monoclonal screening.The specificity and affinity of the monoclonal antibodies and their applications in different immunological experiments were detected.Results:A total of 29 strains of anti-TREM2 monoclonal antibodies were obtained,of which 24 strains could specifically bind to TREM2.The EC50 of antibodies were calculated above nanomolar.These monoclonal antibodies could be used for specific detection of TREM2 in Western blot,immunoprecipitation,flow cytometry and immunofluorescence experiments.Conclusion:Monoclonal anti-bodies against TREM2 with high affinity and specificity are successfully generated,which lay the foundation for the research and the development of antibody drugs targeting TREM2.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective:To explore the time-dependent changes of blood pressure with the increase of exercise intensity and its clinical significance in Cardiopulmonary Exercise Test for female patients with hypertension. Methods:From August, 2018 to August, 2019, 64 patients (hypertension group) who did not take β-receptor blockers and dihydropyridine calcium antagonists were selected from grade 1 and grade 2 hypertension women excluding myocardial ischemia with Cardiopulmonary Exercise Test. And 86 healthy women (non-hypertension group) excluding myocardial ischemia from the same period of Cardiopulmonary Exercise Test were selected as the controls for retrospective analysis. The time-dependent changes of blood pressure with the increase of exercise intensity were compared between two groups. Results:The blood pressures at resting for three minutes, anaerobic threshold and peak were significantly higher in the hypertension group than in the non-hypertension group (Z > 3.306, P < 0.001). There was no significant difference in peak oxygen uptake between two groups (Z = 1.549, P > 0.05). Conclusion:The blood pressure of the patients with grade 1 and grade 2 hypertension is prone to over elevation, who should pay more attention on blood pressure in sports and rehabilitation.

OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.

Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

OBJECTIVETo investigate the abnormal expression of interferon-induced transmembrane protein 3 (IFITM3) in hepatocellular carcinoma (HCC) and the effect of IFITM3 knock-down on the biological behaviors of hepatocellular carcinoma HepG2 cells.

METHODSWestern blot analysis and immunohistochemical staining were used to determine the expression of IFITM3 protein in 60 HCC samples and paired adjacent tissues. A small interfering RNA fragments of IFITM3 (IFITM3 siRNA) was transiently transfected into HepG2 cells and expressions of IFITM3 at mRNA and protein levels were examined by qRT-PCR and Western blotting. The changes in the proliferation of the transfected cells were determined using cell counting kit 8 (CCK8) assay, and the cell invasion and migration were tested using Transwell assay and wound-healing assay.

RESULTSCompared with the adjacent tissues, HCC tissues expressed significantly higher levels of IFITM3. In HepG2 cells, transfection with IFITM3 siRNA resulted in significant down-regulation of IFITM3 expression at both the protein and mRNA levels and obviously suppressed cell proliferation, invasion, and migration ability as compared with the cells transfected with scrambled siRNA and control cells (P<0.05).

CONCLUSIONSIFITM3, which is overexpressed in HCC, plays a vital role in the proliferation and invasion of HCC cells and may serve as a potential target for gene therapy of HCC.

Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Proliferation ; Down-Regulation ; Gene Knockdown Techniques ; Hep G2 Cells ; Humans ; Liver Neoplasms ; genetics ; pathology ; Membrane Proteins ; genetics ; RNA, Messenger ; RNA, Small Interfering ; RNA-Binding Proteins ; genetics ; Transfection

Objective To observe the alterations of each menstrual factor in ovarian aging .Methods The data were obtained from one-year observation of a prospective cohort involving 323 healthy women in the age of 30-54 years in a community in Beijing .Menstrual diary was kept and serum level of follicle-stimulating hor-mone ( FSH) was tested .The participants were divided into groups based on age , FSH level , and stages of repro-ductive aging.Alterations of length of menstrual cycle (LMC), length of menstrual period , and menstrual volume were analyzed in each group .Results Age:the mean LMC extended after the age of 40 years, obviously after 48, and peaked with (67.04 ±36.77) days in≥52-year-old group.The mean length of menstrual period did not vary much with age .However , the variation of mean length of menstrual period gradually increased with age after 44 years old, peaked in 50-to 51-year-old group.The menstrual volume scores were approximately stable between 38 and 47 years of age , with a peak of (45.06 ±93.54) in48 -to 49-year-old group and a minimum of (15.87 ± 13.81) in≥52-year-old group.FSH level:LMC increased with elevation of FSH levels .There was no signifi-cant difference in the mean length of menstrual period among FSH level groups , but the variation of length of menstrual period was maximum in 2040U /Lgroup .Stages of reproductive aging:the length of menstrual period and menstrual volume scores among each stage showed no statistically significant difference ( P>0.05 ) .Co nclusions The LMC altered significant-ly in ovarian aging , which could be used as staging criteria of reproductive aging .The length of menstrual period and menstrual volume are also showing some characteristic changes , possibly of some clinical values .

Objective To investigate the changes of serum sex hormone levels and ovary size in ovarian aging in women living in a Beijing community .Methods A total of 418 healthy women aged 30 to 68 years who could be staged by STRAW +10 staging system were recruited from a Beijing community and prospectively fol -lowed-up for 5 years.Menstrual diary was recorded by every woman during the research .Serum estradiol ( E2 ) and follicle stimulating hormone ( FSH) levels were tested at baseline and 5 years later .Pelvic ultrasonography was performed for measurement of ovary size .Results According to STRAW+10 stage, E2 began to decrease in early postmenopausal stage , which further decreased in late postmenopausal stage .FSH increased significantly from the beginning of late menopausal transition stage , remaining at a high level after menopause .The length , width , and area of the ovary all reduced after menopause .Hormone levels and ovary size changed with some rules in the 5-year follow-up even when the STRAW+10 stage did not change .In women with staging progressed after 5 years of follow-up, E2 and FSH levels, and length, width, and area of the ovary were significantly different ( all P<0.01 ) when progressing from early or late menopausal transition stage to early postmenopausal stage . Ovarian no-echo cyst (diameter ≥1.4 cm and <2.5 cm) was the most common in late menopausal transition stage both at baseline and after 5 years, with an incidence of 6.5% and 12.1%, respectively.Conclusions When the STRAW+10 stage changes from menopausal transition to early postmenopausal stage , E2 decreases and FSH increases significantly with obvious ovarian atrophy .Reproductive aging has more influence on hormone lev-els and ovary size than aging does .STRAW+10 staging system could be applied for women in Beijing .

Objective To explore the impact of menstrual status on musculoskeletal pain in healthy women.Methods A total of 697 generally healthy women aged 35 to 64 years were recruited from a communi-ty in Beijing.Data were collected by face-to-face interview with a questionnaire including social and demo-graphic features, menstrual status, frequency of musculoskeletal pain ( rarely, occasionally, or frequently ) during the last two weeks at neck, lower back, knee, and other parts of the body.Frequent pain was consid-ered severe and its potential relevant factors were analyzed .Results In all the subjects, 33.4%complained of frequent lower back pain, 31.0% frequent knee pain, 29.7% frequent neck pain, and 25.6% pain at other parts.The prevalence of musculoskeletal pain was higher in postmenopausal women than in premenopa-usal women ( P<0.01 ); early postmenopausal women had most frequent musculoskeletal pain , while the frequency declined in late postmenopausal period.The prevalence of neck pain and lower back pain in-creased during the menopausal transition period and was not associated with age .The prevalence of knee pain increased with body mass index ( BMI) and age ( OR=1.085 , 1.050 ) .Overweight and obesity were risk factors for knee pain in women .Logistic regression analysis showed that the odds ratio of knee pain in-creased in obese women ( BMI≥28 kg/m2 ) compared with women with normal BMI ( <24 kg/m2 ) ( OR=2.256 ) .Conclusions Menopause may be an important factor for musculoskeletal pain in women , the associa-tion of musculoskeletal pain with age and BMI also should be considered .