Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m², fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m², male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult ; Aged ; Humans ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Blood Pressure/physiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Antihypertensive Agents/therapeutic use* ; Smoking ; Body Mass Index ; Hypertension/epidemiology*

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC₅₀) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.
Animals ; Zebrafish/metabolism* ; Embryo, Nonmammalian/metabolism* ; Transcriptome ; Oxidative Stress ; Water Pollutants, Chemical/metabolism*

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.
Female ; Humans ; Middle Aged ; Adult ; Aged ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; China ; Adenocarcinoma/pathology* ; Endometrium/pathology* ; Gastrointestinal Neoplasms/pathology* ; Biomarkers, Tumor/analysis*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Objective: To analyze the safety and efficacy of combined left atrial appendage (LAA) and patent foramen ovale (PFO) closure in adult atrial fibrillation (AF) patients complicating with PFO. Methods: This study is a retrospective and cross-sectional study. Seven patients with AF complicated with PFO diagnosed by transesophageal echocardiography (TEE) in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from June 2017 to October 2020 were selected. Basic data such as age, gender and medical history were collected. The atrial septal defect or PFO occluder and LAA occluder were selected according to the size of PFO, the ostia width and depth of LAA. Four patients underwent left atrial appendage closure(LAAC) and PFO closure at the same time. PFO closure was performed during a one-stop procedure of cryoablation combined with LAAC in 2 patients. One patient underwent PFO closure at 10 weeks after one-stop procedure because of recurrent transient ischemic attack (TIA). All patients continued to take oral anticoagulants. TEE was repeated 8-12 weeks after intervention. In case of device related thrombus(DRT), TEE shall be rechecked 6 months after adjusting anticoagulant and antiplatelet drug treatment. Patients were follow-up at 1, 3, 6, 12, 24 months by telephone call, and the occurrence of cardio-cerebrovascular events was recorded. Results: Among the 7 patients with AF, 2 were male, aged (68.0±9.4) years, and 3 had a history of recurrent cerebral infarction and TIA. Average PFO diameter was (3.5±0.8)mm. Three patients were implanted with Watchman LAA occluder (30, 30, 33 mm) and atrial septal defect occluder (8, 9, 16 mm). 2 patients were implanted with LAmbre LAA occluder (34/38, 18/32 mm) and PFO occluder (PF1825, PF2525). 2 patients were implanted with LACbes LAA occluder (24, 28 mm) and PFO occluder (PF2525, PF1825) respectively. The patients were followed up for 12 (11, 24) months after operation. TEE reexamination showed that the position of LAA occluder and atrial septal defect occluder or PFO occluder was normal in all patients. DRT was detected in 1 patient, and anticoagulant therapy was adjusted in this patient. 6 months later, TEE showed that DRT disappeared. No cardiovascular and cerebrovascular events occurred in all patients with AF during follow-up. Conclusions: In AF patients complicated with PFO, LAAC combined with PFO closure may have good safety and effectiveness.
Adult ; Aged ; Atrial Appendage/surgery* ; Atrial Fibrillation/surgery* ; Cardiac Catheterization/methods* ; China ; Cross-Sectional Studies ; Foramen Ovale, Patent/surgery* ; Humans ; Male ; Middle Aged ; Retrospective Studies