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 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 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 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.

Objective:To explore the mediating effect of carotid atherosclerosis on serum triglyceride-glucose (TyG) index and silent lacunar infarction (SLI) in non-diabetic population.Methods:A total of 2 482 patients were selected from the Health Examination Center of Hebei General Hospital from January 2019 to December 2021. The basic demographic information, biochemical parameters, calculated TyG index and carotid plaque score were collected. SLI was diagnosed according to the criteria formulated by Chinese Society of Neurology. Participants were divided into SLI group and non-SLI group according to whether there was SLI in brain magnetic resonance imaging, and the non-SLI group was normal without lacunar infarction. Spearman correlation analysis was used to explore the correlation between TyG index and carotid plaque score. Binary Logistic regression analysis was used to analyze the effects of TyG index and carotid plaque score on SLI. Bootstrap was used to explore whether carotid plaque score mediated the association between TyG index and SLI.Results:There were 471 patients (18.98%) who had SLI, and 2 011 patients (81.02%) did not. Carotid plaque score [2(0, 5) vs 1(0, 3)] and TyG index [7.17(6.81, 7.64) vs 7.12(6.77, 7.54)] were increased in the SLI group compared with the non-SLI group ( Z=-4.213, Z=-2.636, P<0.05). Spearman correlation analysis showed that carotid plaque score was positively correlated with TyG index ( r=0.083, P<0.001). Multivariate Logistic regression analysis indicated that carotid plaque score ( OR=1.047, 95% CI 1.002-1.094) and TyG index ( OR=1.329, 95% CI 1.106-1.598) were independent risk factors for SLI ( P<0.05). Mediated effect analysis showed that TyG index had a direct effect on the incidence of SLI (β=0.265, 95% CI 0.102-0.428). Carotid plaque score partially mediated the effect of TyG index on the incidence of SLI (β=0.024, 95% CI 0.009-0.043), and the mediating effect accounted for 8.30% of the total effects. Conclusion:In non-diabetic population, TyG index and carotid plaque score are predictors of SLI, and the carotid plaque score is a partial mediator in the effect of TyG index on the incidence of SLI.