OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P＝0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P＝0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r＝0.345, P＝0.010) and IL-6 (r＝0.395, P＝0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P＜0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. Conclusion The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Objective:To explore the application effect of patient mutual assistance model guided by the hierarchy of needs theory in patients with acute myocardial infarction.Methods:Using the convenient sampling method, 40 patients with acute myocardial infarction in the Fourth People's Hospital of Haikou from September 2018 to October 2019 were selected as the control group and 40 patients with acute myocardial infarction from November 2019 to January 2021 were selected as the intervention group. The control group implemented the conventional nursing model, and the intervention group implemented the patient mutual assistance model guided by the hierarchy of needs theory on this basis. Perceived Stress Scale (PSS) , SDS and Herth Hope Scale (HHI) were used to evaluate the effect of intervention.Results:After the intervention, the total scores of PSS of patients in the two groups were lower than those before the intervention, and the difference was statistically significant ( P<0.01) . And the total PSS score of the intervention group was lower than that of the control group, and the difference was statistically significant ( P<0.01) . After the intervention, the total SDS score of patients of the two groups was lower than that before the intervention, and the difference was statistically significant ( P<0.01) . And the total SDS score of the intervention group was lower than that of the control group, and the difference was statistically significant ( P<0.01) . After intervention, the scores of HHI dimensions and total scores in two groups were higher than before intervention, and the differences were statistically significant ( P<0.01) . The scores of HHI dimensions and the total score of the intervention group were higher than those in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The patient mutual assistance model guided by the hierarchy of needs theory can effectively reduce the self-perceived pressure of patients with acute myocardial infarction after PCI, improve their depression and increase the level of hope.

Objective:To evaluate the value of shear wave elastography (SWE) and salivary gland ultrasound scoring(SGUS) system in the diagnosis of salivary glands lesions in patients with Sj?gren′s syndrome(SS) and to compare the diagnostic efficiency of the two methods.Methods:From June 2019 to November 2020, Fifty-eight patients with suspected SS were selected from the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University. According to the 2002 American-European Consensus Group classification standard, the enrolled patients were divided into two groups: SS group (47 cases) and non-SS group(11 cases). According to symptom duration, SS group was divided into the ≤5 years group (29 cases) and the >5 years group (18 cases). Meanwhile, 40 healthy volunteers were enrolled in this study as normal control group. The diagnostic value of salivary gland ultrasound scoring system and Young′s modulus in SS were analyzed.Results:The differences in Young′s modulus of parotid gland and submandibular gland between SS group and non-SS group (or control group) were statistically significant (all P<0.05). The ultrasound score of SS group was significantly higher than that of non-SS group and control group (all P<0.05). SGUS and Young′s modulus were not significantly different between different course groups (all P>0.05). The areas under ROC curve of the mean Young′s value in parotid and submandibular gland and the SGUS were 0.801, 0.829 and 0.676, respectively. The comparison of the area under the curve between the Young′s modulus of the parotid and submandibular glands and the ultrasound score was statistically significant (all P<0.05). Conclusions:SWE and Ultrasonography scoring system have certain value in the diagnosis of salivary gland lesions in SS, and can provide important reference information for clinical diagnosis from different perspectives. The diagnostic efficiency of SWE for salivary glands lesions in patients with SS is better than that of SGUS scoring system.

Objective To evaluate the efficacy,safety of rigid gas permeable contact lens (RGPCL) wearing for over 5 years in different degrees of keratoconus eyes.Methods A retrospective case study was performed.The clinical data of 217 eyes with different degree of keratoconus from 126 keratoconus patients who fitted with RGPCL in Beijing Tongren Hospital from 2000-2010 over 5 years were analyzed.The eyes were divided into mild keratoconus group (Ks≤45.0 D),moderate keratoconus group (45.0 D＜ Ks ＜ 52.0 D) and severe keratoconus group (Ks ≥52.0 D) according to the severity.Uncorrected visual acuity (UCVA,LogMAR),spectacle corrected visual acuity (SCVA) and RGP corrected visual acuity (RGPVA) was examined before RGPCL wearing and the end of followingup after RGPCL wearing.The refraction,corneal curvature,corneal astigmatism were measured with auto-refractomer/keratometer and keratoconus screening analysis system of computer-assisted corneal topography.Comparisons of the changes of corrected visual acuity and corneal parameters were assessed.Results The RGPVA was 0.09±0.17,0.05±0.07 and 0.07 ±0.07 in the mild,moderate and severe keratoconus group,respectively,showing a significant difference among the three groups (F=0.522,P=0.594);The △Ks was (2.25±5.42),(0.26±3.44) and (-4.52±3.44)D,and △Kf was (2.06±4.98),(1.02±3.41) and (-2.03±5.05)D,and the change value of corneal astigmatism was (0.19±2.87),(-0.78±2.84) and (-2.44±3.77)D in the mild,moderate and severe keratoconus group(all at P＜ 0.05),respectively,with the minimum amount of change in the severe keratoconus group.The variation of differential sector index (△DSI) was-0.33 ± 1.64,0.14±3.01 and-2.11 ±4.28;the variation of center/ surround index (△CSI) was-0.41 ± 1.07,0.03±2.22 and-2.49±4.15;the variation of standard deviation of power (△SDP) was-0.43 ±0.64,-0.02 ±0.89 and-1.67 ± 1.68;the variation of keratoconus prediction index (△KPI)was 0.00±0.07,0.03±0.09 and-0.05±0.11 in the mild,moderate and severe keratoconus group,respectively,and the reduced amount in above parameters was much more in the severe keratoconus group than that in the mild and moderate keratoconus group (all at P＜0.01).Mild conjunctivitis and corneal affection occurred in 12 eyes (5.5％)during the follow-up.Conclusions Long-term wearing RGPCL can improve the visual acuity and slow the tendency of corneal curvature increase in keratoconus eyes,and this procedure is safe and effective for the correction of different degree of keratoconus.

Objective To explore the in vitro culture methods for oriented differentiation of peritoneal cells and bone marrow cells into high-purity mast cells,and to identify the function of these mast cells.Methods Peritoneal cells and bone marrow cells were isolated from the peritoneal cavity lavages and femur of C57BL/6 mice,and cultured with both interleukin-3 (IL-3) and stem cell factor for 2 and 4 weeks respectively.Light microscopy was performed to observe the morphology of these cells,toluidine blue staining to identify the degree of maturity of these mast cells,and flow cytometry to measure the expression of cell surface markers C D 117 and FceR Ⅰ α.After the stimulation with compound 48/80 at different concentrations,the degranulation rate of mast cells was counted under the microscope,and β-hexosaminidase release rate was measured by spectrophotometry.Results After 2-or 4-week culture,the mouse peritoneal and bone marrow cells all manifested as refractive suspension cells of uniform size.Toluidine blue staining showed violaceous metachromatic granules in the cytoplasm of the two kinds of cells.The proportions of CD117 or FcεR Ⅰ α single-positive peritoneal and bone marrow-derived mast cells were all more than 95％,and the proportions of CD117/FcεR Ⅰ α double-positive peritoneal and bone marrow-derived mast cells were 97.68％ ± 0.80％ and 96.12％ ± 0.76％ respectively.The degranulation rates of mast cells in the 100-and 1 000-mg/L compound 48/80 groups significantly differed from those in the blank control group (all P ＜ 0.01).Compared with the blank control group,the β-hexosaminidase release rates significantly increased in bone marrow-derived mast cells in the 100-mg/L compound 48/80 group and peritoneal mast cells in the 10-and 100-mg/L compound 48/80 groups (P ＜ 0.01 or 0.05).Conclusion IL-3 and stem cell factor can co-induce the directed differentiation and proliferation of mouse bone marrow stem cells and peritoneal cells,so as to harvest highnuritv mature degranulated mast cells,and lay a foundation for subsequent cell biology research.

Objective: To analyze the microvessel density (MVD) and lymph node metastasis in the papillary thyroid carcinoma (PTC) with punctate or sheet calcification. Methods: Fifty PTC patients in the Affiliated Hospital of Yangzhou University from May 2015 to October 2017 were retrospectively enrolled in this study. All of the 50 PTC patients were divided into punctate calcification group (38 cases) and sheet calcification group (12 cases) according to the different features of pathological calcification in microscope examination. For the two groups, the central and peripheral zone MVD and the lymph node metastasis of each PTC nodule were compared. Results: For PTC nodules of punctate calcification group, the mean central and peripheral zone MVD were (51±7)/HP and (64±8)/HP, respectively. For those of sheet calcification group, which were (35±5)/HP and (49±6)/HP, respectively. The mean MVD in both central and peripheral zone of PTC nodules of punctate calcification group were significantly higher than those of the sheet calcification group (t values were 10.183 and 12.406, both P < 0.05). The neck Ⅵ area lymph node metastasis rates of the punctate and sheet calcification groups were 42.1% (16/38) and 8.3% (1/12), respectively. The lymph node metastasis rate of the punctate calcification group was significantly higher than that of the sheet calcification group (χ ² = 4.635, P < 0.05). Conclusion PTC nodules with different type of pathological calcification may have different invasion and metastasis, and PTC with punctate calcification is more likely to undergo local metastasis than PTC with sheet calcification.

Objective To measure the levels of plasma D-dimer,activated coagulation factor Ⅶ (FⅦa) and activated clotting factor Ⅻ (FⅫa) in patients with chronic urticaria (CU),and to investigate their relationship with the occurrence of CU.Methods Venous blood samples were collected from 50 patients with CU and 50 healthy human controls.Dry-column immune scattering chromatography was performed to detect the plasma level of D-dimer,and enzyme-linked immunosorbent assay (ELISA) to measure the levels of FⅦa and FⅫa.In addition,autologous plasma skin test (APST) was conducted in 43 patients with CU,and autologous serum skin test (ASST) in 41 patients with CU.A correlation analysis was carried out between the above three parameters and disease severity as well as between the results of APST and ASST and plasma level of D-dimer.Results The levels of plasma D-dimer and F Ⅶa were significantly higher in patients with CU than in healthy human controls (both P ＜ 0.05),while no significant difference was found in FⅫa level between the two groups (P ＞ 0.05).Moreover,the degree of increase in D-dimer plasma level was positively correlated with disease severity in the patients with CU.The plasma level of D-dimer was significantly higher in APST-positive patients than in APST-negative patients (P ＜ 0.05),but not significantly different between ASST-positive and-negative patients (P ＞ 0.05).Conclusions Coagulation mechanism,especially the extrinsic coagulation pathway,is related to the occurrence of CU.Studies on coagulation mechanism are beneficial to the evaluation of severity,and clinical treatment,of CU.

Objective To explore the diagnostic significance of CT and MRI in dermatofibrosarcoma protuberans.Methods Analyze the CT and MRI images of 16 cases which were confirmed as dermatofibrosarcoma protuberans by pathology.The medical imaging features of dermatofibrosarcoma protuberans were summarized.In the total 16 cases(including 6 male cases,10 female cases),15 cases had suffered from dermatofibrosarcoma protuberans for more than 1 year, 11 cases for more than 5 years, and 9 cases had history of recurrence.Results On MRI, the mass was slightly hypointense on T 1 WI, inhomogeneously hyperintense on T 2 WI with inhomogenous enhancement.The diameters of mass were less than 5 cm in 3 cases,and were more than 5cm in 13 cases.Fifteen cases had clear demarcation between the masses and their adjacent muscles , 7 cases had “suspension sign” in shapes, 10 cases had “sub-nodules outward” features at the edge of the tumors , 12 cases had “multinodular” features inside the tumor , and 8 tumors grew into the surrounding fat layer like roots.Conclusion Dermatofibrosarcoma protuberans can be diagnosed accurately based on the features displayed on CT and MRI.