北京大学学报（医学版）最新文献

Objective: To evaluate the efficacy of cyclophosphamide (CYP) at different doses in replicating the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) in an animal model, thereby providing an experimental basis for understanding the pathophysiology of IC/BPS and assessing treatment strategies.

Methods: Twenty-eight female Sprague-Dawley rats aged seven weeks were divided into four groups: Group a (25 mg/kg CYP), group b (75 mg/kg CYP), group c (125 mg/kg CYP), and group d (a control group). The rats were injected intraperitoneally with either CYP or saline solution. Evaluations included urine spot tests, von Frey filament pain threshold tests, urodynamic examinations, and histological assessments.

Results: The study found that the 25 mg/kg CYP dosage significantly outperformed higher doses in simulating bladder dysfunction and inflammatory responses while minimizing the impact on the rats' physiological functions. Specifically, urine spot area, group a showed a significant reduction in urine spot area compared with the control group (P < 0.05), while groups b and c did not show significant differences. Pain threshold: The von Frey filament test indicated increased visceral pain in group a, aligning closely with IC/BPS patient symptoms, without a significant increase in urination frequency. Urodynamic assessments: Group a exhibited decreased bladder compliance and reduced maximum bladder capacity (P < 0.05), with no significant differences in baseline bladder pressure and maximum detrusor pressure across all groups. Histological analysis: Hematoxylin-eosin (HE) staining revealed that bladder tissue in group a had moderate inflammatory reactions, whereas groups b and c showed severe inflammation and tissue damage, correlating with the higher doses of CYP. Furthermore, the urine spot tests and von frey filament tests provided quantitative data supporting the model's reliability, urine spot count, group a had an average urine spot count of (15±3) spots, significantly higher than the control group's (5±2) spots (P < 0.01). Nociceptive score: Group a nociceptive score increased to 0.5±0.1, indicating heightened pain sensitivity compared with the control group 0.10±0.05 (P < 0.01).

Conclusion: The 25 mg/kg CYP demonstrated significant advantages in simulating the key features of non-ulcerative IC/BPS, summarizing the main aspects of the human condition, including persistent visceral pain and mild inflammatory reactions in bladder tissue. These findings offer substantial experimental support for drug development and treatment research in IC/BPS and provide new insights into the complex patho-physiology of the disease.

Objective: To study the distribution characteristics of natural killer (NK) cells and their subsets in normal peripheral blood in China, and to explore their normal value and significance.

Methods: In this study, peripheral blood was collected from 200 healthy adults. Their age range was 18-87 years. All the subjects were divided into 6 age groups: 18-30, 31-40, 41-50, 51-60, 61-70, and 71-87 years. With CD16, CD56, CD4, CD19, as surface markers, fluid cytology detection techniques were used to detect NK cells and the relative and absolute counts. SPSS 27.0 was used for systematic analysis of the data, and the measurement data were expressed as mean±standard deviations. A t test, variance analysis or rank sum test were performed to compare the differences between the age groups and the sex groups. The significance level was set at α=0.05, and P < 0.05 was considered statistically significant.

Results: The range of NK B cells in the 200 healthy adult subjects was (0.46±0.24)×10⁶/L, that of CD3^-CD56⁺NK cells was (13.14±7.56)×10⁶/L, that of CD56^dimCD16⁺NK cells was (5.23±3.12)×10⁶/L, that of CD56^brightNK cells was (85.61±7.40)×10⁶/L, and that of NK T cells was (4.16±3.34)×10⁶/L. There were no statistically significant differences in CD3^-CD56⁺NK cells and NK T cells with respect to age (P= 0.417, P=0.217). However, there was a decreasing trend in the number of NK B cells and CD56^dimCD16⁺NK cells with increasing age (r=0.234, P < 0.001; r=0.099, P < 0.001), particularly after the age of 50. Conversely, CD56^brightNK cells showed an increasing trend with age (r=0.143, P < 0.001).

Conclusion: The detection of NK cells and their subsets has significant reference value for the diagnosis, treatment, and prognosis of autoimmune diseases, infectious diseases, and tumors. This study provides a preliminary reference range for clinical detection of NK cell subsets, but further research with a larger sample size and multi-center trials are needed to confirm these findings.

Objective: To assess the reliability, and validity of the Chinese version of a short-form of Health Literacy Dental scale (HeLD-14) in 3-6 years old preschool children's parents.

Methods: The study population consisted of those eligible 3-6 years old preschool children's parents in Yanqing District, Beijing, China in 2021. A total of 1 479 preschool children's parents were surveyed by questionnaire to understand the general situation of parents and oral health literacy related content. SPSS 21.0 and Mplus 7.4 were used for statistical analysis. Through Cronbach's α coefficient, confirmatory factor analysis, Pearson correlation calculation, Student's t test and other methods, the internal consistency reliability, structure validity, calibration validity and discrimination validity of the scale were evaluated.

Results: The Cronbach's α coefficient of Chinese version HeLD-14 scale was 0.958, and Cronbach's α coefficient of different constructs ranged from 0.778 to 0.963. The confirmatory factor analysis showed that the factor loadings of each item of the Chinese version HeLD-14 scale were between 0.719 and 0.977 (P < 0.001), root-mean-square error of approximation (RMSEA)=0.04, comparative fix index (CFI)=0.992, Tucker-Lewis index (TLI)=0.988, and the model had good goodness of fit. The total score of the Chinese version HeLD-14 scale and the scores of the dimension of concerning, understanding, supporting, financial burden, medical treatment, communication, and application were all positively correlated with general self-efficacy, and the correlation coefficients were 0.439, 0.406, 0.370, 0.344, 0.346, 0.367, 0.373, 0.390, respectively (P all < 0.05). For parents in the high group with the top 27% HeLD-14 score, the average HeLD-14 score was 69.27±1.06, which was higher than the low group with the bottom 27% HeLD-14 score, 41.29±11.09 (t=48.13, P < 0.01).

Conclusion: The Chinese version HeLD-14 scale has good reliability and validity in the 3-6 years old preschool children's parents, and can be used as a tool to assess the oral health literacy of parents of preschool children.

With the continuous development and maturity of anti-tumor immunotherapy technology, immune checkpoint inhibitors as one of the main methods of immunotherapy were increasingly widely used in clinical tumor cases, bringing new hope for many advanced cancer patients with poor response to traditional treatment, but at the same time, reported on adverse reactions of various organs related to this were also increasing, and the immune damage caused by them was harmful to patients, especially immune checkpoint inhibitor-associated pneumonia, immune checkpoint inhibitor-associated myocarditis and immune checkpoint inhibitor-associated encephalitis, which could even seriously endangered the lives of patients. Therefore, it was necessary for clinicians to fully understand and master the mechanism, clinical characteristics, laboratory and imaging examination characteristics, diagnostic criteria and differential diagnosis conditions, and treatment principles of adverse reactions that may be caused by immune checkpoint inhibitors, so as to find a more optimized anti-tumor treatment regimen and actively prepared for the treatment of possible immune-related adverse reactions. In this paper, we reported a case of immune checkpoint inhibitor-associated severe pneumonia, referred to the relevant guidelines, introduced its clinical features, laboratory and imaging findings, difficulties encountered in the diagnosis and treatment process, briefly analyzed the causes, and reviewed the possibility of immune-related pneumonia should be considered when respiratory symptoms occurred in patients receiving immunotherapy; the increased ratio of blood neutrophil count to lymphocyte count, and the increased ratio of eosinophil count to lymphocyte count could be used as indicators to indicate immune-related adverse reactions in patients; bronchoalveolar lavage fluid examination and bronchoscopy and lung biopsy were helpful for the diagnosis; when immune checkpoint inhibitor-associated severe pneumonia occurred, in addition to symptomatic and sup-portive treatment, adequate glucocorticoid-based immunosuppressive therapy should be given in time, and combined with cytokines monoclonal antibodies and other biological agents, immunoglobulin co-therapy, but the current indications for the use of biological agents were not fully clear, and the use of high-dose immunosuppressive drugs might cause the risk of severe infection. Therefore, according to the relevant literature and the findings in the process of clinical diagnosis and treatment, this paper proposed that the serum levels of IL-6, TNF-α, CRP and other inflammatory mediators in patients may be used as a quantitative indication to initiate biological agent therapy and accumulate experience for better solving similar problems in the future.

Objective: To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) modified by miR-125b-5p on systemic lupus erythematosus (SLE).

Methods: The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells (PBMCs) from SLE patients and health checkers. Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs. MRL/lpr mice in each group were injected with UC-MSCs via tail vein, and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks. The expression levels of interleukin (IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA. Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.

Results: miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls (P < 0.01). Compared with the UC-MSCs group, the expression of miR- 125b-5p in UC-MSCs modified by miR-125b-5p group was increased (P < 0.01). The survival rate of UC-MSCs was significantly increased by miR-125b-5p (P < 0.01). Compared with the untreated group of MRL/lpr mice, the expression level of IL-4 in serum was increased (P < 0.05); the expression level of IL-17A was decreased (P < 0.05); the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased (P < 0.05); the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.

Conclusion: UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.

Objective: To analyze the risk factors for postoperative pathological upgrade of prostate cancer patients with single core positive biopsy, and to attempt to build a mathematical model for predicting postoperative pathological upgrade in these cancer patients with single core positive biopsy.

Methods: A retrospective analysis was conducted on 1 349 patients diagnosed with prostate cancer and undergoing radical prostatectomy at Peking University First Hospital from January 2015 to August 2020. The patients' age, body mass index, clinical stage, prostate imaging reporting and data system (PI-RADS) scores, prostate volume in magnetic resonance imaging (MRI), Gleason score of biopsy, serum prostate specific antigen (PSA) before biopsy and operation, surgical method and pathological stage were inclu-ded in the analysis. The variables with P < 0.1 in univariate analysis were included to construct multi-variate Logistic regression and the nomogram was drawn. The model was evaluated using the receiver operating curve.

Results: A total of 71 patients were included in this research, with 34 patients in the upgraded group and 37 patients in the non-upgraded group. There were no significant differences in the patients' age (P=0.585), body mass index (P=0.165), operation method (P=0.08), prostate volume in MRI (P=0.067), clinical stage (P=0.678), PI-RADS score (P=0.203), difference of PSA density (P=0.063), Gleason score in biopsy (P=0.068), PSA before puncture (P=0.359) and operation (P= 0.739) between the two groups. However, there were significant differences in the proportion of tumor tissue (P=0.007), postoperative pathological stage (P < 0.001) and postoperative Gleason score (P < 0.001) between the two groups. The preoperative variables with a P value of less than 0.1 (prostate volume in MRI, difference of PSA density, proportion of tumor tissue and Gleason score in biopsy) in univariate analysis were included in the Logistic regression, and the nomogram was drawn. Only the prostate volume in MRI had a P value of less than 0.05. The area under the curve of the model was 0.773.

Conclusion: In patients with single core positive biopsy, if the prostate volume is small or the proportion of tumor in positive core is small, clinicians should be alert to the possibility of postoperative pathology upgrading, preoperative risk stratification should be carefully considered for patients with possible pathological upgrading. This model can be used to predict the pathological upgrade of patients with single core positive biopsy.

Air embolism is a rare but dreaded complication of medical or surgical procedures with significant mortality. An abnormal air-to-blood pressure gradient and communication between the vein and atmosphere can lead to the venous air embolism. Here, we presented a rare case of venous air embolism just after the removal of the central venous catheters. A 59-year-old female was admitted to Peking University International Hospital suffering from neuromyelitis optica spectrum disorder. After 5 rounds of immunosorbent therapy, her hemodialysis catheter was removed. Five hours later, she suddenly experienced shortness of breath, dizziness, weakness of the lower extremities, transient loss of consciousness and seizures. Ultrasound showed a small amount of gas in the right internal jugular vein and brain CT showed scattered air accumulation in part of venous blood ducts and bilateral cavernous sinuses, which was diagnosed as air embolism. High-flow oxygen inhalation, compression of the right neck extubation site, head down and feet up left decubitus position, intravenous fluid therapy were used. The patient gradually improved and returned to normal activities after one week. To sum up, air embolism is a rare, but serious and life-threatening complication after central catheters removal. Clinicians need to be alerted and take appropriate preventive measures.

Objective: To assess the impact of exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM_2.5) on non-accidental mortality under different apparent temperature levels and to further explore the modification effect of apparent temperature.

Methods: This study used time-series design. Tianjin and Ningbo from China, Bangkok and Chiang Mai from Thailand were selected as the research sites, and the apparent temperature was applied as the exposure index. Through the quantitative estimation of the threshold temperature, the corresponding pollutant concentration was divided into high and low levels, and the generalized Poisson additive model was used to evaluate the association between PM_2.5 exposure and non-accidental death of residents at different temperature levels.

Results: The ave-rage concentrations of PM_2.5 in Tianjin, Ningbo, Bangkok, and Chiang Mai during the study period were (73.6±35.6), (48.0±32.1), (33.5±28.4) and (32.6±28.6) μg/m³, respectively; the average daily non-accidental death counts were 148, 57, 28, and 8. The analysis of the generalized Poisson additive model showed that the daily non-accidental death counts increased by 0.43% (95%CI: 0.33%-0.54%) per 10 μg/m³ increase of PM_2.5 in lag 0 day in Tianjin of China; 0.27% (95%CI: 0.08%-0.46%) per 10 μg/m³ increase of PM_2.5 in lag 2 days in Ningbo of China. The effect was magnified in high temperature levels in Tianjin and in low temperatures in Ningbo and Bangkok. The mortality effect of PM_2.5 in various temperature levels stayed still in co-pollutant regression models.

Conclusion: Exposure to fine particulate matter had an adverse effect on non-accidental mortality, which reminded us to give further attention to the pollution control. The findings also indicated that apparent temperature might modify mortality effects of PM_2.5 and the modification effect varied in different regions. Protective policies due to regional differences should be made and more scientific and social attention on mutual effect of air pollution and climate change needs to be appealed.

Objective: To understand the growth and development of Uygur primary and secondary school students aged 7-18 years in Xinjiang from 1985 to 2019, and to provide theoretical basis for formulating health promotion strategies.

Methods: In the study, 18 591 Xinjiang Uygur primary and secondary school students aged 7-18 years with complete body height, body mass and body mass index (BMI) data by the Chinese National Surveillance on Students' Constitution and Health in 1985, 2000, 2010 and 2019 were selected as the research objects. The growth rate of each age group in each adjacent two survey years and per decade were calculated, and a t-test on the mean of each index to analyze was used to analyze the difference between the years.

Results: During the period 1985-2019, except for the height of girls aged 17-18 years, the height and mass of Uyghur boys and girls in all the age groups increased significantly (P all < 0.01), and the growth range of height for boys and girls was 2.06-9.89 cm and -0.03 to 6.86 cm, respectively; the growth range of mass was 2.39-10.2 kg and 2.57-8.05 kg, respectively; the BMI for most age groups increased from 2000 to 2019, whose range was -0.94 to 0.86 kg/m² and 0.08-1.34 kg/m² for boys and girls, respectively. The growth range was greater for boys than for girls. Height and mass of boys and girls increased at the fastest rate in the first 15 years; the height of most age groups, mass and BMI of a few age groups decreased in the middle 10 years; overall turned to a positive growth trend in the last 9 years except for the mass of boys, and height of girls increased at the highest rate in all periods. Advancement of maximum increase/growth age (MIA) in height was greater than that in mass and BMI for girls; MIA in height did not change significantly in boys, but MIA in mass and BMI was significantly earlier.

Conclusion: The overall body shape indexes of Uyghur primary and secondary school students aged 7-18 years in Xinjiang during the 34 years showed an increasing trend with gender differences. The overall status of growth was in the early stage of a secular growth trend, requiring focused attention to the mass status of both sexes to prevent the emergence of abnormal nutritional status.

Objective: To evaluate the level of first morning voided (FMV) urinary luteinizing hormone (LH) in girls with breast development, and to determine the value of FMV urine LH in the evaluation of central precocious puberty (CPP).

Methods: From September 2018 to April 2021, among the patients who were admitted to the Department of Pediatrics of Peking University Third Hospital for "precocious puberty" and underwent gonadotropin-releasing hormone (GnRH) stimulation test, a total of 108 girls were enrolled. According to CPP diagnostic criteria, they were divided into CPP group (n=45) and non-CPP group (n=63). The clinical characteristics and hormone levels of the two groups were compared. Receiver operating characteristic (ROC) curve was used to analyze the cut-off value of FMV urinary LH in the diagnosis of CPP in girls. Further analyses were done to evaluate the value of FMV urinary LH in the diagnosis of CPP using correlation analysis between urinary LH level and common clinical cha-racteristics.

Results: ROC curve analysis showed that FMV urine LH level was significant for the diagnosis of CPP. The cut-off value of FMV urine LH was 0.69 IU/L (specificity 56.9%, sensitivity 85.0%, area under curve 0.804, P < 0.001). The basic clinical characteristics without GnRH stimulation test were analyzed by binary Logistic regression analysis, indicating that the level of FMV urine LH, uterine volume, ovarian volume and advanced T-bone age had predictive significance for CPP diagnosis in girls (OR values were 2.125, 1.961, 1.564 and 2.672, respectively). The prediction model was established and the area under the ROC curve was 0.904, P < 0.001. The level of FMV urine LH was positively correlated with the levels of serum LH, FSH and estrogen before GnRH stimulation test, the peak value of blood LH after GnRH stimulation test, T bone age and uterine volume, with r values of 0.462, 0.373, 0.242, 0.360, 0.373 and 0.263, respectively, and P values were < 0.001, < 0.001, 0.013, < 0.001, < 0.001 and 0.007, respectively.

Conclusion: FMV urine LH can provide a good indication for the diagnosis of CPP. Combining with bone age advanced level and pelvic ultrasound measurement, the predictive value of FMV urine LH can be further improved for the diagnosis of CPP in girls.