Objective To investigate the expression and significance of CCR9/CCL25 pathway in acute rejection of mouse skin transplantation.Method BALB/c mice and C57BL/6 mice were selected as allogeneic and syngeneic skin graft donors and C57BL/6 as recipients,then established a murine skin transplantation model of acute rejection.Allogeneic transplant recipient mice were injected with an AntiCCL25(2 g,as experimental group) mAb or IgG(2 g,as control group) every other day via tail vein,a total of 10 injections.The transplanted graft was scored visually daily,and then we collected skin graft and spleen from recipient mice of each group at 3,5,7 days after transplantation.HE staining was done to analyze necrosis of skin tissue Confocal and immunohistochemistry were also used to measure CCR9 and CCL25 expression in recipient skin grafts.Result HE staining indicated that there was a widespread inflammatory cell infiltration in the skin from allo-transplantation mice,and CCR9 expression measured by immunohistochemistry and confocal was significantly elevated in the surface of the infiltrated CD3 + T cells from skin grafts tissue and spleen.Neutralization of CCL25 with Anti-CCL25 mAb significantly prolonged allogra,ft survival and markedly reduced inflammation.Conclusion CCR9 was highly expressed in the spleen and skin grafts tissue of allogeneic transplanted mice Neutralization of CCL25 by intravenous injection of Anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival.Our study indicates that CCR9/CCL25 pathway is involved in acute rejection process of skin transplantation model in mice were used as syngeneic and skin grit skin graft donor mice.

Objective:To evaluate 131I adjuvant therapy in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutant patients with non-distant metastatic papillary thyroid cancer (PTC). Methods:From January 2008 to January 2019, a total of 181 PTC patients (65 males, 116 females, age: (38.9±11.8) years) with non-distant metastases from Peking Union Medical College Hospital were retrospectively enrolled. All patients received only one time 131I therapy with complete clinicopathological information, data of follow-up (median time: 63 months) and assessment of response to therapy. Patients were divided into mutant and wild type group in terms of BRAF V600E status or ablation group (1.1 GBq) and adjuvant therapy group (3.7-5.5 GBq) in terms of different 131I dosage. Clinicopathological features and the response to therapy were compared between different groups by using independent-sample t test, Mann-Whitney U test and χ2 test. Results:The levels of preablative stimulated thyroglobulin (ps-Tg) in the BRAF V600E mutant type group ( n=150) was significantly higher than that in the wild type group ( n=31; 6.32(0.90, 8.70) vs 3.92(0.40, 4.40) μg/L; z=-2.413, P=0.016), however, there were no significant differences in other clinicopathological characteristics (including age, sex, tumor size, multifocality, capsule invasion and N staging) between the two groups ( t=-0.663, z=-1.151, χ2 values: 0.003-1.491, all P>0.05) and the therapeutic response was also not different between the two groups( χ2=1.094, P=0.778). Of 81 patients who received 131I adjuvant therapy, the ps-Tg level of BRAF V600E mutant type group ( n=69) was higher than that of the wild type group( n=12; 8.70(1.30, 11.80) vs 3.40(0.30, 4.50) μg/L; z=-2.194, P=0.028), while the therapeutic response was not different between the two groups ( χ2=1.792, P=0.617). Compared with BRAF V600E mutant patients received 131I ablation ( n=81), BRAF V600E mutant patients received 131I adjuvant therapy ( n=69) had larger tumors (1.52(0.95, 2.00) vs 1.21(0.60, 1.50) cm; z=-2.728, P=0.006), more advanced N staging ( χ2=11.460, P=0.003) and higher ps-Tg level (8.70(1.30, 11.80) vs 4.34(0.50, 5.30) μg/L; z=-3.314, P=0.001), but the therapeutic response was not different between the two groups ( χ2=6.478, P=0.091). Conclusion:131I adjuvant therapy may improve the longer-term response to therapy in BRAF V600E mutant PTC patients with lager tumors, more advanced N staging and higher ps-Tg level.

Objective To observe the splenocytes immune response elicited by different concentrations of recombinant Toxo?plasma gondii profilin(rTgPRF)through the nasal route,and determine the optimal dose. Methods Fifty female BALB/c mice were randomly divided into 5 groups. The immunized groups were intranasally administered with 10,20,30μg or 40μg of rTgPRF that was separately dissolved in 20μl of phosphate?buffered saline(PBS)on days 0,14,and 21 respectively,while the control mice were given PBS solution instead. Two weeks after the last immunization,all mice were killed. Under asceptic conditions,the spleens from the immunized mice were dissected,and then the splenocyte proliferative responses in vitro were tested by CCK?8 kit. The levels of IFN?γ,IL?2,IL?4 and IL?10 of splenocyte culture supernatant were detected by ELISA. Re?sults Compared to the control group,the splenocytes from the 30μg and 40μg groups exhibited a significantly higher prolifer?ative response to rTgPRF(P<0.05),and SI from the 30μg rTgPRF group was higher than that from the 40μg group(P<0.05). The levels of IFN?γin all the immunized groups(P<0.05)and IL?2 in the 20,30μg and 40μg groups were significant?ly stronger than those in the control(P<0.05),and the 30μg group presented the highest concentrations of IFN?γ(P<0.01) and IL?2(P<0.01). There were no statistical differencesa mong the groups in the levels of IL?4 and IL?10. Conclusions The intranasal immunization with rTgPRF can induce the splenocyteproliferation and Th1?type mediated immunity. The best immu?nized dose is confirmed as 30μg.

OBJECTIVE:To observe the clinical efficacy and safety of Buzhong yiqi wuling decoction combined with western medicine in the treatment of chronic congestive heart failure(CHF). METHODS:120 CHF patients were divided into observation group and control group by random number table method,with 60 cases in each group. Control group received conventional western medicine treatment as rest,low salt diet and diuretics. Observation group was additionally given Buzhong yiqi wuling decoction,one dose a day,at twice,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Average TCM symptom score, level of plasma NT-proBNP,6 min walk test(6MWT)distance before and after treatment,clinical efficacy and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in average TCM symptom score,level of plasma NT-proBNP and 6MWT distance between 2 groups(P>0.05). After treatment,average TCM symptom score and level of plasma NT-proBNP of 2 groups were decreased significantly,and the observation group was more significant than the control group,with statistical significance(P<0.05);6MWT distance of 2 groups were improved significantly compared to before treatment,and the observation group was significantly longer than the control group,with statistical significance(P<0.05). After treatment,total effective rate of observation group(93.33%)was significantly higher than that of control group(83.33%),with sta-tistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Buzhong yiqi wuling decoction is an ef-fective prescription to treat CHF,and can relieve clinical symptoms,improve the cardiac function,decrease NT-proBNP level and en-hance the patient exercise tolerance with good safety.

OBJECTIVETo assess the association of methylenetetrahydrofolate reductase (MTHFR) gene 677C to T polymorphism with blood homocysteine (Hcy) level among women of childbearing age from Shiyan area.

METHODSPCR-chip hybridization was used to determine the genotype of MTHFR 677C to T, and a biochemical assay was used to determine the total Hcy level among 428 healthy women of childbearing age. Association of MTHFR 677C to T with total Hcy level was assessed.

RESULTSHeterozygous CT mutation was most common form for the MTHFR 677C to T polymorphisms and amounted for 49.77% among the group, while the CC wild type and homozygous TT mutation respectively accounted for 30.61% and 19.63%. These gave a frequency of 44.51% for the 677T allele. The dominant genotype among different age groups were the CT type. Of note, the proportion of MTHFR 677CC is higher in women above 30 years of age. The distribution of MTHFR 677C to T genotypes has differed significantly among different age groups (P<0.05). Compared with those with wild type alleles, carriers of MTHFR mutations had a higher plasma Hcy level. The genotypic frequencies of MTHFR C677T in Shiyan region differed significantly from those of Sichuan, Hebei, Henan and Shandong (P<0.05) but were similar to those of Jiangsu, Guangdong, Ningxia and Xinjiang.

CONCLUSIONThe distribution of MTHFR C677T polymorphism among women of childbearing age in Shiyan area is influenced by age and is geographically specific and associated with plasma Hcy level. Nearly 50% of women have carried the high risk alleles, for whom folic acid supplementation is crucial for the reduction of birth defect rate.

Objective To systematically review the risk prediction models for intradialytic hypotension in maintenance hemodialysis patients,with a view to provide references for clinical practice.Methods PubMed,Embase,Web of Science,Cochrane Library,CINAHL,CNKI,VIP,Wanfang and CBM were searched from inception to May 29,2023.2 reviewers independently screened the literature,extracted information and assessed methodological quality using the Prediction Model Risk of Bias Assessment Tool.Results A total of 20 studies and 25 models were included with the sample size of 68～9 292 cases and the incidence of outcome events of 2.1～51％.Baseline systolic blood pressure,age,ultrafiltration rate,diabetes and dialysis duration were the top 5 predictors of repeated reporting of the models.20 models reported the area under the curve of ranging from 0.649 to 0.969,and 5 models reported calibration metrics.There were 9 internal validations and 4 combined internal and external validation models.The overall applicability of the 20 studies was good,but all had a high risk of bias,mainly in data analysis.Conclusion Research on risk prediction models for intradialytic hypotension in maintenance hemodialysis patients is still in the developmental stage.Future studies should improve the research design and reporting process,and validation studies of existing models should be carried out to further evaluate the effectiveness and feasibility in clinical practice.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To investigate the diagnostic value and cutoff value of the basal luteinizing hormone (LH) level for central precocious puberty (CPP) in girls with different body mass index (BMI) values.Methods:A total of 1 087 girls aged 6 to 8 years old with breast development and visiting the Department of Endocrine Genetics and Metabolism, Fuzhou Children′s Hospital of Fujian Medical University from January 2014 to December 2018 were enrolled.The girls had the breast development of Tanner stage B2 or B3.They were divided into groups of normal weight (840 cases), overweight (133 cases) and obesity (114 cases) according to BMI percentiles corresponding to their age and sex.All individuals underwent gonadotropin-releasing hormone (GnRH) agonist test.Statistical analysis was performed using SPSS 18.0 software, and the receiver operating characteristic (ROC) curve was drawn.Results:In the normal weight group, 393 girls were positive and 447 girls were negative for GnRH test.In the overweight group, 72 girls were positive and 61 girls were negative for GnRH test.In the obesity group, 40 girls were positive and 74 girls were negative for GnRH test.The areas under the ROC curve (AUC) of the basal LH level for the diagnosis of CPP in the normal weight, overweight, and obese girls were 0.826, 0.774, and 0.801, respectively.When the Youden index was maximum, the cutoff values of the basal LH level were 0.245 IU/L, 0.225 IU/L and 0.145 IU/L, respectively; the sensitivities were 63.9%, 65.3%, and 80.0%, respectively; the specificities were 87.9%, 82.0%, and 71.6%, respectively.When the cutoff value of the basal LH level was 0.455 IU/L in the normal weight group, 0.480 IU/L in the overweight group, and 0.335 IU/L in the obesity group, the specificities of the 3 groups were all above 96.6%.Conclusions:It is reliable to use the basal LH level for CPP diagnosis for girls with different BMI values.The cutoff value of the basal LH level for CPP diagnosis in obese girls is the lowest.

Objective:To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated by apatinib.Methods:A retrospective study was performed on apatinib-treated (phase Ⅱ) patients ( n=19; 9 males, 10 females; age 46.0 (41.0, 57.5) years) with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022. The relationships between serum thyroglobulin (Tg) and response evaluation criteria in solid tumors (RECIST) 1.1 structural imaging efficacy evaluation and disease progression trend were analyzed. The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data. Results:During the median 49.41 months follow-up, the baseline Tg was 363.20(13.08, 2 490.50) μg/L. The Tg time-to-response was 0.47(0.47, 0.98) months, which was 1.80 (1.30, 1.90) months for RECIST 1.1. After 2, 4 and 8 weeks of initial treatment, the median Tg of the whole cohort decreased by 38.68%, 64.70% and 78.94%, respectively. After 8 weeks, the reducing degree of maximum diameter of target lesions was 33.48%. According to the best response, patients were divided into two groups: partial response (PR) group ( n=15) and stable disease (SD) group ( n=4). The median decreasing degree of Tg in PR group and that in SD group were 87.00% and 28.79%, and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00% and 21.22%. According to the final efficacy evaluation, patients were further divided into two groups: progressive disease (PD) group ( n=13) and non-PD (including PR and SD) group ( n=5). The median increasing degree of Tg in PD group was higher than that in non-PD group (381.55% vs 175.43%; U=10.00, P=0.037). The increasing degree of Tg and that of the maximum diameter of target lesions were 167.31% and 2.14% after the 1st adjustment, which were 231.06% and 9.73% after the 2nd adjustment. The differences of changes in Tg and maximum diameter of target lesions before and after the 1st dose adjustment were statistically significant ( z values: -3.06 and -2.23, P values: 0.002 and 0.026). Conclusion:During the apatinib treatment of RAIR-DTC, Tg can reflect the therapeutic effect of apatinib earlier than traditional imaging (RECIST 1.1), indicating the disease progression trend more sensitively.