1.Effects and Mechanisms of Zhenxin Anshen Prescription on 1-Chloro-2,4-Dinitrobenzene-Induced Atopic Dermatitis Mice Based on ORAI1/NFAT Signaling Asix
Ruoxi CHEN ; Shanshan JIANG ; Jie YANG ; Xiaoyu YANG ; Ruiyao XU ; Lin FANG ; Yiding ZHAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):168-173
Objective To investigate the effects and mechanisms of Zhenxin Anshen Prescription(composed of Os Draconis,Ostreae Concha,Lophatheri Herba,Drynariae Rhizoma,Poria)on mice with atopic dermatitis(AD)based on the calcium channel regulator 1(ORAI1)/nuclear factor of T-cells(NFAT)signalling axis.Methods Thirty-six BALB/c mice were randomly divided into a blank control group,a model group,a Cetirizine group(1.3 mg·kg-1)and a Zhenxin Anshen Prescription group(36.36 g·kg-1),with nine mice in each group.AD mouse model was established using 1-chloro-2,4-dinitrobenzene(DNCB)induction.The drug was administered by gavage once a day for 2 weeks.At the end of drug administration,the area of skin lesions was measured and the severity of skin lesions was scored;spleen mass was measured and spleen index was calculated;pathological changes of skin lesion tissues were observed by HE staining;interleukin 4(IL-4),IL-13 and thymic stromal lymphopoietin(TSLP)in serum were detected by ELISA;and the protein expression levels of ORAI1,calmodulin phosphatase A(CaN)and nuclear factor of T cells 2(NFAT2)were detected by Western Blot.Results Compared with the blank control group,the skin lesion score of mice in the model group was significantly increased(P<0.01),the skin lesion area was significantly enlarged(P<0.01);the thickness of the epidermis and dermis were significantly increased(P<0.01),hyperkeratosis of the epidermis,hypertrophy of the stratum spinosum,and infiltration of inflammatory cells such as eosinophils and lymphocytes can be seen in the dermis;the splenic index and serum IL-4,IL-13,TSLP levels were significantly increased(P<0.01);protein expression levels of CaN,NFAT2,ORAI1 were significantly increased in the skin lesion tissues(P<0.01).Compared with the model group,the dermatitis score of mice in the Zhenxin Anshen Prescription group was significantly decreased(P<0.01),the lesion area was significantly reduced(P<0.01),the epidermal and dermal thicknesses(P<0.01),the hyperkeratosis of epidermis was alleviated,the spinous layer was slightly hypertrophic,and there was a small amount of inflammatory cell infiltration in the dermis;the splenic index and the levels of serum IL-4,IL-13,and TSLP were significantly decreased(P<0.01);the protein expressions levels of CaN,NFAT2,and ORAI1 in the skin lesion tissues were significantly decreased(P<0.01).Conclusion Zhenxin Anshen Prescription can ameliorate dermatopathological injury in DNCB-induced AD mice,and the mechanism may be related to its ability to inhibit the protein expressions of ORAI1,CaN and NFAT2,reduce the levels of serum type 2 inflammatory factors TSLP,IL-4 and IL-13,and ameliorate cutaneous inflammation and itching through immunomodulation.
2.The re-elevation of parathyroid hormone level after successful operation for primary hyperparathyroidism
Ruiyao YANG ; Anyang LIU ; Bin LUO
Chinese Journal of General Surgery 2023;38(10):754-759
Objective:To explore the probability, influencing factors, and management strategies of the re-increase of parathyroid hormone (PTH) in patients with primary hyperparathyroidism (pHPT) after successful surgery.Methods:A retrospective analysis of the clinical data of 40 pHPT patients treated at Beijing Tsinghua Chang Gung Hospital from Jan 2016 to Mar 2021 was conducted.Results:Of the 40 pHPT patients, 21 (53%) experienced a re-increase of PTH after surgery, but their serum calcium levels were normal and no new parathyroid lesions were found on neck ultrasonography. Univariate analysis showed that there were significant differences in tumor diameter, preoperative PTH level, preoperative serum calcium level, and preoperative alkaline phosphatase level between the postoperative PTH re-increase group and the normal group ( t=-2.042, P=0.045; t=-2.600, P=0.013; t=-2.223, P=0.043; t=-2.162, P=0.037). Regression analysis showed that preoperative PTH level >236 ng/L was an independent risk factor for postoperative PTH re-increase ( OR=5.180, 95% CI: 1.032-25.995). Vitamin D deficiency was common among pHPT patients (88%), and there was a negative correlation between preoperative PTH and 25-hydroxy vitamin D levels. After vitamin D supplementation, the PTH levels of four patients with postoperative PTH re-increase returned to normal. Conclusions:The probability of PTH re-increase in pHPT patients after successful parathyroidectomy was 53%, and most cases occurred in the short term after surgery (within 8 weeks), but it did not indicate disease recurrence. A higher preoperative PTH level was an independent risk factor for postoperative PTH re-increase. Vitamin D deficiency was more common among pHPT patients, and correction of vitamin D deficiency can help restore normal PTH levels after surgery.