Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective To evaluate the clinical efficacy of Zhuyun Yangmo Formula(composed of Dioscoreae Rhizoma,Corni Fructus,Cinnamomi Cortex,Cuscutae Semen,Chuanxiong Rhizoma,Angelicae Sinensis Radix,Lycii Fructus,Rehmanniae Radix Praeparata,Polygonati Rhizoma,Asini Corii Colla,Rubi Fructus,etc.)combined with Letrozole for the treatment of patients with infertility caused by follicular maldevelopment(FM)of kidney deficiency and blood stasis syndrome type.Methods Sixty patients with FM-caused infertility of kidney deficiency and blood stasis syndrome type treated at the Reproductive Medicine Department of Qingyuan Hospital of Traditional Chinese Medicine from February 2024 to August 2024 were randomized into a control group(30 cases,treated with Letrozole alone)and an observation group(30 cases,treated with Zhuyun Yangmo Formula plus Letrozole)for three menstrual cycles.Primary outcomes of maximum diameter of preovulatory follicles and serum levels of estradiol(E2),luteinizing hormone(LH),and follicle-stimulating hormone(FSH)in the two groups were observed before and after treatment.After treatment,the pregnancy rates in the two groups were compared.Results After treatment,serum E2,LH and FSH levels in both groups were significantly increased compared to those before treatment(P＜0.05),and the observation group showed significantly greater increase than the control group,with statistically significant differences(P＜0.01).(2)After treatment,both groups showed improvement in the maximum diameter of preovulatory follicles compared to that before treatment(P＜0.05),and the observation group demonstrated significantly better improvement than the control group,with a statistically significant difference(P＜0.01).(3)After 3 menstrual cycles of treatment,the pregnancy rate in the observation group was 40.00%(12/30),significantly higher than 16.67%(5/30)in the control group,with a statistically significant difference(P＜0.05).Conclusion Zhuyun Yangmo Formula combined with Letrozole demonstrates superior efficacy in improving follicular development,elevating serum E2,LH and FSH levels,and increasing pregnancy rates in patients with FM-caused infertility of kidney deficiency and blood stasis syndrome type when compared to Letrozole monotherapy alone.

Objective To evaluate the clinical efficacy of Yishen Pojian Formula(YSPJF)combined with Letrozole in treating infertility due to ovulatory dysfunction in polycystic ovary syndrome(PCOS)patients of kidney deficiency and blood stasis type.Methods Sixty PCOS patients diagnosed as ovulatory-dysfunction-induced infertility(kidney deficiency and blood stasis type)at the Reproductive Medicine Department of Qingyuan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from February 2024 to December 2024 were randomized into an observation group and a control group using a random number table,with 30 cases in each group.The control group received Letrozole alone,while the observation group received YSPJF combined with Letrozole.Both groups were treated for three menstrual cycles and followed up for three months.The changes in traditional Chinese medicine(TCM)syndrome scores,serum levels of sex hormones[follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),and anti-Müllerian hormone(AMH)],ovarian function parameters[antral follicle count(AFC),maximum follicle diameter(FD),and endometrial thickness(EM)]in the two groups were observed.Moreover,the ovulation rate and pregnancy rate were compared.Results(1)After treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the serum FSH of the two groups was higher than that before treatment(P＜0.05),and the levels of serum LH,T,and AMH were lower than those before treatment(P＜0.05),and the increase of the serum FSH level and the decrease of the levels of serum LH,T,and AMH in the observation group were significantly superior to those in the control group,the differences being all statistically significant(P＜0.05).(3)After treatment,AFC was reduced(P＜0.05)and FD and EM were elevated(P＜0.05)in both groups compared with those before treatment,and the reduction of AFC and the elevation of FD and EM in the observation group were significantly superior to that in the control group(P＜0.05).(4)After treatment,the ovulation rate and pregnancy rate of the observation group were 90.00%(27/30)and 50.00%(15/30),respectively,which were higher than those of the control group[70.00%(21/30)and 30.00%(9/30)],and the differences were statistically significant(P＜0.05).Conclusion YSPJF combined with Letrozole exerts significant clinical efficacy for PCOS patients with infertility due to ovulatory dysfunction of kidney deficiency and blood stasis type,and the combined therapy is effective on alleviating TCM syndromes,modulating sex hormone levels,improving ovarian function,and elevating ovulation rate and pregnancy rate.

OBJECTIVE: To explore whether streptococcal infection may aggravate renal damage in children with Henoch-Schönlein purpura nephritis and its possible mechanism. METHODS: In the study, 485 children diagnosed with Henoch-Schönlein purpura nephritis from July 2015 to December 2019 were selected to analyze their clinical data retrospectively. According to the diagnosis of discharge, whether it was combined with streptococcal infection, the children were divided into two groups. The experimental group contained 91 children with Henoch-Schönlein purpura nephritis combined with streptococcal infection, and there were 394 children who were not infected with Streptococcus in the control group. Suitable test items were preliminarily selected through artificial neural network, and then data analysis was performed through SPSS 23.0. RESULTS: The children with Henoch-Schönlein purpura nephritis infected with streptococcus had statistically significant differences compared with the uninfected children in the test items of urine protein, liver and kidney function, immunoglobulin and complement. Anti-streptolysin O had mild correlation with IgG (Spearman r=-0.328), fibrin degradation products (Spearman r=-0.207), total protein (Spearman r=-0.202) and globulin (Spearman r=-0.223). Compared with the children who were not infected with streptococcus, the differences of the average levels of age (P=0.001), IgG (P < 0.001), fibrin degradation products (P=0.019), total protein (P < 0.001), globulin (P < 0.001), IgA (P < 0.001), IgM (P=0.003), complement 3 (P=0.016), complement 4 (P=0.002), albumin/globulin ratio (P=0.007), alkaline phosphatase (P=0.036), and estimated glomerular filtration rate (P=0.039) in the infected children were statistically significant. In order to explore the risk factors of kidney damage in the children with Henoch-Schönlein purpura nephritis, Logistic regression was performed using anti-streptolysin O, age, immunoglobulin and complement as independent variables, urine protein detection parameters, liver and kidney functions as dependent variables. Age ≤10 years old and hypocomplementemia might be risk factors for aggravating renal damage in the children with Henoch-Schönlein purpura nephritis. CONCLUSION Streptococcal infections may aggravate renal damage in children with Henoch-Schönlein purpura nephritis, in which hypocomplementemia, inflammation, fibrinolysis and disorders of coagulation perhaps play an important role. Children with streptococcal infection should be treated with anti-infective treatment in time and necessarily, and followed up after discharge regularly.
Humans ; IgA Vasculitis/complications* ; Streptococcal Infections/complications* ; Child ; Male ; Female ; Nephritis/microbiology* ; Retrospective Studies ; Child, Preschool ; Kidney/pathology* ; Adolescent

Purpose To investigate the 18F-FDG PET/CT metabolic characteristics and the accuracy of diagnosis in post-traumatic osteomyelitis. Materials and Methods A total of 64 patients with post-traumatic fracture nonunion and suspected infection in Beijing Jishuitan Hospital were retrospectively analyzed. The PET/CT examinations were performed from May 2019 to April 2020. Qualitative and semi-quantitative evaluation methods were used to evaluate the diagnostic accuracy of 18F-FDG PET/CT in post-traumatic osteomyelitis. The diagnostic efficiency was compared among different laboratory indexes,such as erythrocyte sedimentation rate,C-reactive protein and leukocyte. Logistic regression was used to analyze parameters with diagnostic significance. Results Among 64 patients with post-traumatic fracture nonunion,37 were ultimately diagnosed with post-traumatic osteomyelitis. Among them,23 were confirmed through positive microbial cultures during surgery,and 14 were diagnosed based on clinical symptoms and follow-up results. The remaining 27 patients showed no signs of infection based on intraoperative microbial cultures (n=10) or clinical follow-up of more than six months (n=17). PET/CT correctly identified infections in 34 of the 37 infected cases and accurately ruled out infections in 23 of the 27 non-infected cases. The sensitivity,specificity,positive predictive value,negative predictive value and overall diagnostic accuracy of PET/CT were 91.89％,85.19％,89.47％,88.46％ and 89.06％,respectively. The maximum standardized uptake value (SUVmax) of PET/CT semi-quantitative parameter in the infection group (6.23±2.16) was higher than that in the non-infection group (4.24±1.86),showing a statistically significant difference (t=3.864,P<0.01). Logistic regression analysis revealed that SUVmax and C-reactive protein had diagnostic significance for distinguishing between groups,and SUVmax demonstrated higher diagnostic accuracy than C-reactive protein (x2=27.245,P<0.001). Conclusion The metabolic imaging features provided by 18F-FDG PET/CT imaging help to provide a more accurate reference for the diagnosis of post-traumatic osteomyelitis,which is worthy of clinical application.

Androgenetic alopecia (AGA) is currently the most common hair loss disease, which is the result of a combination of genetic and environmental factors, and manifests itself as miniaturization of hair follicles around the top of the head and frontotemporal region, which eventually leads to hair reduction or disappearance. The pathogenesis of AGA is closely related to a variety of signaling pathways, which include the Wnt/β-catenin signaling pathway, bone-forming protein (BMP) signaling pathway, insulin-like growth factor (IGF) signaling pathway, fibroblast growth factor (FGF) signaling pathway, hedgehog (SHH) signaling pathway, and so on. Several cytokines are involved in these signaling pathways, including β-catenin, BMP2, IGF-1, and FGF5. An in-depth study of AGA-related signaling pathways and related cytokines can help to provide a comprehensive understanding of the pathogenesis of AGA, provide a certain theoretical basis for the discovery of new signaling pathways, and provide a new research direction for the treatment of AGA.

Androgenetic alopecia (AGA) is currently the most common hair loss disease, which is the result of a combination of genetic and environmental factors, and manifests itself as miniaturization of hair follicles around the top of the head and frontotemporal region, which eventually leads to hair reduction or disappearance. The pathogenesis of AGA is closely related to a variety of signaling pathways, which include the Wnt/β-catenin signaling pathway, bone-forming protein (BMP) signaling pathway, insulin-like growth factor (IGF) signaling pathway, fibroblast growth factor (FGF) signaling pathway, hedgehog (SHH) signaling pathway, and so on. Several cytokines are involved in these signaling pathways, including β-catenin, BMP2, IGF-1, and FGF5. An in-depth study of AGA-related signaling pathways and related cytokines can help to provide a comprehensive understanding of the pathogenesis of AGA, provide a certain theoretical basis for the discovery of new signaling pathways, and provide a new research direction for the treatment of AGA.

Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.

Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P＜0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.