Objective To explore the model of decreased ovarian reserve(DOR)induced by experimental autoimmune thyroiditis(EAT)in mice and investigate the protective mechanism of Jiexu Zichong Granules(ZCWS).Methods Ninety-six Kunming female mice were randomly divided into the J control group,BIW control group,J model group,and BIW model group.The mice were immunized with antigen(0.1 mg,once or twice per week)combined with high iodine water(0.64 g/L)for 7-19 weeks to validate the model.Subsequently,30 mice were randomly divided into the ZCWS group,model group,and control group.The DOR model was established by immunization with the antigen(0.2 mg per week)combined with high iodine water feeding for 13 weeks.The ZCWS group received oral administration of traditional Chinese medicine suspension(0.64 g/mL),while the remaining groups received an equivalent volume of physiological saline for 7 weeks.Thyroid and ovarian tissue morphology and related indicators were detected using HE staining,ELISA,IHC,and Western blot.Results Antigen immunization for 13 weeks(0.1-0.2 mg per week)combined with high iodine water feeding stably constructed the EAT DOR model.ZCWS reduced thyroid lymphocyte infiltration,follicular structure destruction,and serum TPOAb and TGAb levels(P<0.01).It inhibited MDA activity(P<0.01),increased GSH-Px and SOD activities(P<0.05),increased primordial,primary,and secondary follicles(P<0.05),and reduced atretic follicles(P<0.01).ZCWS upregulated AMH and downregulated FSH(P<0.01),regulated the expression of Bcl-2,Bax,and Caspase-3 proteins in ovarian tissue,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05).It upregulated Bcl-2 protein(P<0.05),downregulated Bax(P<0.01),and Caspase-3(P<0.05)proteins,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05)in ovarian tissue.Conclusion ZCWS improves ovarian reserve function in EAT mice by activating the Nrf2 pathway,inhibiting oxidative stress,and reducing follicular atresia.

[Objective]To investigate the efficacy and safety of Double-Flower Moisturizing Ointment occlusive dressing therapy in treating vascular endothelial growth factor receptor-tyrosine kinase inhibitors(VEGFR-TKIs)induced hand-foot skin reactions(HFSR).[Methods]A total of 58 cancer patients with HFSR induced by VEGFR-TKIs,who were treated at The First Affiliated Hospital of Zhejiang Chinese Medical University from October 8,2021 to December 31,2024,were enrolled in this study.Using a randomized single-blind design,they were assigned to either an observation group(29 cases)or a control group(29 cases).The observation group received oral vitamin B6 combined with Double-Flower Moisturizing Ointment occlusive dressing therapy,while the control group received oral vitamin B6 combined with base ointment occlusive therapy.Both groups were treated for 14 consecutive days.The total effective rate of HFSR management,pain relief rate,quality of life improvement,differences in efficacy between syndrome types and the incidence of adverse reactions were compared between the two groups.[Results]The total effective rate was significantly higher in observation group(89.7%)than in control group(58.6%).The observation group demonstrated a markedly superior overall pain relief rate of 76.9%,which was significantly higher than the 38.5%achieved in control group.Similarly,the quality of life improvement rate in observation group(44.8%)was markedly higher than that in control group(13.8%),with all differences being statistically significant(P<0.05).In the two main syndrome types of damp-heat stagnation and heat-toxicity accumulation on the skin,the observation group exhibited a significantly greater total effective rate compared to control group(P<0.05).No cutaneous adverse reactions or abnormal liver and kidney function were observed in either group.[Conclusion]Double-Flower Moisturizing Ointment occlusive therapy is effective in managing VEGFR-TKIs-induced HFSR.It demonstrates superior outcomes over base ointment occlusive dressing therapy in terms of the overall response rate,pain relief and quality of life improvement,particularly among patients presenting with damp-heat stagnation or heat-toxicity accumulation on the skin.Furthermore,this treatment modality exhibits a favorable safety profile,indicating high clinical application value.

Objective To exploring the drug rules for treating children's night cough based on the theory of"Shaoyang as the pivot".Methods 189 cases of children with night cough were included,and 224 prescriptions.Used the Traditional Chinese Medicine Inheritance Assistance Platform to analyze the time distribution,syndrome types,and four nature,five flavors,and channel tropism of diseases.Used frequency statistics,association rule analysis,and cluster analysis to extract drug patterns for pediatric night cough.Results Coughing occured most frequently during the Yin period.The syndrome type was mainly Shaoyang syndrome.The high-frequency core drugs were Chaihu,Huangqin,and Banxia,etc..The prescription characteristics were Xiaochaihu decoction without Renshen,Shengjiang,and Dazao,and added Wuweizi,Danggui and Xingren.The drugs were used flexibly according to the syndromes:Maxing Er San decoction was added to the phlegm and drink syndrome,Qumai Er Chen decoction was added to the food stagnation syndrome,Sijunzi decoction was added to the qi deficiency syndrome,Maiwei Dihuang decoction was added to the yin deficiency syndrome,and Weijing decoction was added to the phlegm and heat syndrome.Conclusion Based on the basic principle of harmonizing Shaoyang,and according to the disease mechanism,the classical prescription is flexibly used,forming a night cough treatment system based on the"Shaoyang as the pivot"theory,with distinct clinical characteristics.

[Objective]To investigate the efficacy and safety of Double-Flower Moisturizing Ointment occlusive dressing therapy in treating vascular endothelial growth factor receptor-tyrosine kinase inhibitors(VEGFR-TKIs)induced hand-foot skin reactions(HFSR).[Methods]A total of 58 cancer patients with HFSR induced by VEGFR-TKIs,who were treated at The First Affiliated Hospital of Zhejiang Chinese Medical University from October 8,2021 to December 31,2024,were enrolled in this study.Using a randomized single-blind design,they were assigned to either an observation group(29 cases)or a control group(29 cases).The observation group received oral vitamin B6 combined with Double-Flower Moisturizing Ointment occlusive dressing therapy,while the control group received oral vitamin B6 combined with base ointment occlusive therapy.Both groups were treated for 14 consecutive days.The total effective rate of HFSR management,pain relief rate,quality of life improvement,differences in efficacy between syndrome types and the incidence of adverse reactions were compared between the two groups.[Results]The total effective rate was significantly higher in observation group(89.7%)than in control group(58.6%).The observation group demonstrated a markedly superior overall pain relief rate of 76.9%,which was significantly higher than the 38.5%achieved in control group.Similarly,the quality of life improvement rate in observation group(44.8%)was markedly higher than that in control group(13.8%),with all differences being statistically significant(P<0.05).In the two main syndrome types of damp-heat stagnation and heat-toxicity accumulation on the skin,the observation group exhibited a significantly greater total effective rate compared to control group(P<0.05).No cutaneous adverse reactions or abnormal liver and kidney function were observed in either group.[Conclusion]Double-Flower Moisturizing Ointment occlusive therapy is effective in managing VEGFR-TKIs-induced HFSR.It demonstrates superior outcomes over base ointment occlusive dressing therapy in terms of the overall response rate,pain relief and quality of life improvement,particularly among patients presenting with damp-heat stagnation or heat-toxicity accumulation on the skin.Furthermore,this treatment modality exhibits a favorable safety profile,indicating high clinical application value.

Objective To exploring the drug rules for treating children's night cough based on the theory of"Shaoyang as the pivot".Methods 189 cases of children with night cough were included,and 224 prescriptions.Used the Traditional Chinese Medicine Inheritance Assistance Platform to analyze the time distribution,syndrome types,and four nature,five flavors,and channel tropism of diseases.Used frequency statistics,association rule analysis,and cluster analysis to extract drug patterns for pediatric night cough.Results Coughing occured most frequently during the Yin period.The syndrome type was mainly Shaoyang syndrome.The high-frequency core drugs were Chaihu,Huangqin,and Banxia,etc..The prescription characteristics were Xiaochaihu decoction without Renshen,Shengjiang,and Dazao,and added Wuweizi,Danggui and Xingren.The drugs were used flexibly according to the syndromes:Maxing Er San decoction was added to the phlegm and drink syndrome,Qumai Er Chen decoction was added to the food stagnation syndrome,Sijunzi decoction was added to the qi deficiency syndrome,Maiwei Dihuang decoction was added to the yin deficiency syndrome,and Weijing decoction was added to the phlegm and heat syndrome.Conclusion Based on the basic principle of harmonizing Shaoyang,and according to the disease mechanism,the classical prescription is flexibly used,forming a night cough treatment system based on the"Shaoyang as the pivot"theory,with distinct clinical characteristics.

Objective To explore the model of decreased ovarian reserve(DOR)induced by experimental autoimmune thyroiditis(EAT)in mice and investigate the protective mechanism of Jiexu Zichong Granules(ZCWS).Methods Ninety-six Kunming female mice were randomly divided into the J control group,BIW control group,J model group,and BIW model group.The mice were immunized with antigen(0.1 mg,once or twice per week)combined with high iodine water(0.64 g/L)for 7-19 weeks to validate the model.Subsequently,30 mice were randomly divided into the ZCWS group,model group,and control group.The DOR model was established by immunization with the antigen(0.2 mg per week)combined with high iodine water feeding for 13 weeks.The ZCWS group received oral administration of traditional Chinese medicine suspension(0.64 g/mL),while the remaining groups received an equivalent volume of physiological saline for 7 weeks.Thyroid and ovarian tissue morphology and related indicators were detected using HE staining,ELISA,IHC,and Western blot.Results Antigen immunization for 13 weeks(0.1-0.2 mg per week)combined with high iodine water feeding stably constructed the EAT DOR model.ZCWS reduced thyroid lymphocyte infiltration,follicular structure destruction,and serum TPOAb and TGAb levels(P<0.01).It inhibited MDA activity(P<0.01),increased GSH-Px and SOD activities(P<0.05),increased primordial,primary,and secondary follicles(P<0.05),and reduced atretic follicles(P<0.01).ZCWS upregulated AMH and downregulated FSH(P<0.01),regulated the expression of Bcl-2,Bax,and Caspase-3 proteins in ovarian tissue,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05).It upregulated Bcl-2 protein(P<0.05),downregulated Bax(P<0.01),and Caspase-3(P<0.05)proteins,downregulated Keap1 protein(P<0.01),and upregulated Nrf2(P<0.01),HO-1,and LONP1 proteins(P<0.05)in ovarian tissue.Conclusion ZCWS improves ovarian reserve function in EAT mice by activating the Nrf2 pathway,inhibiting oxidative stress,and reducing follicular atresia.

Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function, and is one of the microvascular complications of diabetes. With the in-depth understanding of the pathogenesis of DN, the role of intestinal flora imbalance in the disease has been found clinically. This suggests that restoring the host′s healthy gut flora may be a means of improving DN. In fact, recent studies have shown that many of the drugs currently used to treat DN affect gut microbiota composition. In this review, intestinal flora is regarded as one of the main factors affecting the development of DN, and DN therapy targeting intestinal flora is summarized to provide new ideas for the diagnosis and treatment of DN.