Objective: To explore the relationship between nuclear factor-kappa B subunit 1 (NFKB1) and LIM-homeobox gene 2 (LHX2) polymorphisms and esophageal cancer susceptibility, so as to provide the reference for the prevention and treatment of esophageal cancer. Methods: A total of 100 patients with primary esophageal cancer diagnosed at the Affiliated Tumor Hospital of Xinjiang Medical University from 2019 to 2023 were selected as the case group, and 100 healthy individuals undergoing physical examination during the same period of time were selected as the control group. Demographic information, disease history and lifestyle data were collected through questionnaire surveys. The single nucleotide polymorphisms at the rs28362491 and rs4648068 loci of NFKB1 gene as well as rs10760310 and rs10121751 loci of LHX2 gene were detected using multiplex high-temperature ligase detection reaction technology. The relationship between these loci and esophageal cancer susceptibility were analyzed using a multivariable conditional logistic regression, linkage disequilibrium and haplotype analysis. The impact of the interaction between the above-mentioned loci and environmental factors on esophageal cancer susceptibility using the generalized multifactor dimensionality reduction (GMDR) method. Results: The case group comprised 73 males and 27 females, with a mean age of (64.02±8.90) years. The control group included 73 males and 27 females, with a mean age of (64.54±9.43) years. The genotype distributions of rs28362491, rs4648068, rs10760310 and rs10121751, loci in both groups conformed to Hardy-Weinberg equilibrium (all P>0.05). Multivariable conditional logistic regression analysis showed that rs10760310 and rs10121751 loci of LHX2 gene were associated with the esophageal cancer susceptibility (both P<0.05). The overdominant model of rs10760310 loci of LHX2 gene had the lowest Akaike information criterion value (OR=0.22, 95%CI: 0.10-0.47). GAA haplotypes at rs4648068, rs10760310 and rs10121751 loci were associated with a lower risk of esophageal cancer susceptibility (OR=0.26, 95%CI: 0.13-0.50). GMDR analysis revealed a statistically significant interaction between rs10760310 loci and smoking on esophageal cancer susceptibility (P<0.05, cross-validation consistency coefficient: 10/10). Conclusion The rs10760310 and rs10121751 loci polymorphisms of LHX2 gene may be associated with esophageal cancer susceptibility, and there is an interaction between rs10760310 loci and smoking on the esophageal cancer susceptibility.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective: To evaluate the clinical efficacy of preimplantation genetic testing for monogenic disorders(PGT-M) in families with hereditary epilepsy. Methods : Whole-exome sequencing(WES) and familial co-segregation analysis were performed to validate the pathogenicity of variants(PCDH19 c. 1031C > G and LGI1 c. 856T >G) in two monogenic epilepsy families. A clinical PGT-M pathway was implemented,and reproductive outcomes were tracked. Results: In Family 1(PCDH19 likely pathogenic variant),13 blastocysts were biopsied over two ovarian stimulation cycles,yielding 3 unaffected euploid embryos(23. 1%). After the third frozen embryo transfer,a healthy male infant was successfully delivered. Prenatal diagnosis confirmed that the fetus did not carry the pathogenic variant PCDH19. Family 2(LGI1 variant of uncertain significance,VUS) screened 14 blastocysts,identifying 2 unaffected euploid embryos(14. 3%),with the first transfer unsuccessful. A clinical pregnancy was currently ongoing following the second frozen-thawed embryo transfer(FET). Conclusion PGT-M can precisely block the vertical transmission of monogenic epileptic pathogenic variants,offering an effective reproductive intervention strategy for families with hereditary epilepsy.

【Objective】 To investigate the development of the foot arch and develop a rehabilitation treatment plan for children with spastic diplegia of cerebral palsy gross motor function classification(GMFCS) system grade Ⅰ-Ⅱ. 【Methods】 Fifty children with spastic diplegia and flat exostosis with GMFCS grade Ⅰ-Ⅱ were selected into this study, and were divided into observation group (n=25) and control group (n=25) using the random number table method. The control group received conventional exercise therapy, while the observation group received arch correction exercises additionally. Both groups underwent treatment once a day for 5 days a week. Children in both groups were evaluated before and 6 months after the intervention. The arch index F, electronic plantar pressure measurement index, and the D and E scores of the Gross Motor Function Measure (GMFM-88) were used to assess the severity of clubfoot and the level of motor development. 【Results】 Bofore intervention, there were no significant differences in the arch index F, electronic plantar pressure measurement index, and GMFM-88 score between the observation group and the control group (P>0.05). After 6 months of intervention, the scores of arch index F(t=9.89, 5.35), and GMFM-88 (t=6.59, 3.46) in both groups increased significantly(P<0.05). The scores of foot arch index F (26.08±0.73) and GMFM-88 (30.24±7.94) in the observation group and control group were significantly higher than those in the control group (25.34±0.64, 25.20±7.06) (t=3.81, 2.37, P<0.05). Plantar pressure pictures showed a gradual increase in lateral foot pressure compared to medial pressure, and a decrease in pressure in the midfoot arch area, indicating a decrease in foot valgus and progressive development of the arch. 【Conclusion】 The comprehensive rehabilitation therapy technique incorporating arch correction and gymnastics treatment can promote the arch development in children with GMFCS grade Ⅰ-Ⅱ spastic diplegia, which is important for improving their foot and ankle function and motor development level.

OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer （NSCLC） from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data， with a cycle of 3 weeks， a research deadline until 99% of patients die， and an annual discount rate of 5%. The model outputs were total cost， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Taking 3 times China’s per capita gross domestic product （GDP） in 2023 as the willingness-to-pay （WTP） threshold， the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib （observation group） versus erlotinib alone （control group） in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan， ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY， which was more than 3 times China’s per capita GDP in 2023 （268 074 yuan/QALY） as the WTP threshold， indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab， the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY， the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone， bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， when using 3 times China’s per capita GDP in 2023 as the WTP threshold.

OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer （NSCLC） from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data， with a cycle of 3 weeks， a research deadline until 99% of patients die， and an annual discount rate of 5%. The model outputs were total cost， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Taking 3 times China’s per capita gross domestic product （GDP） in 2023 as the willingness-to-pay （WTP） threshold， the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib （observation group） versus erlotinib alone （control group） in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan， ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY， which was more than 3 times China’s per capita GDP in 2023 （268 074 yuan/QALY） as the WTP threshold， indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab， the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY， the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone， bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， when using 3 times China’s per capita GDP in 2023 as the WTP threshold.

Objective To investigate the clinical effects and pregnancy outcomes of using luteal phase long protocol and GnRH antagonist protocol in patients with polycystic ovary syndrome(PCOS)who have failed their first GnRH antagonist protocol therapy.Methods The clinical data of 163 PCOS patients who underwent IVF/ICSI-ET were retrieved.After the failure of their first GnRH antagonist protocol treatment,they were divided into two groups in the second controlled ovarian hyperstimulation(COH)cycle:Luteal phase long protocol group(n=95)and Gn-RH antagonist protocol group(n=68).A retrospective analysis and comparison of basic clinical data,clinical and laboratory indicators,and pregnancy outcomes between two groups were conducted.Results ① There was no sta-tistically significant difference in basic clinical indicators between two group except LH.② Compared the first and second cycle treatments of patients in the luteal phase long protocol group,the initiation dose of gonadotropin(Gn),total number of Gn days,total Gn usage,estradiol(E2)on the day of hCG injection,number of retrieved eggs,oocyte maturation rate,2PN fertilization rate,2PN cleavage rate,blastocyst formation rate,high-quality blas-tocyst formation rate,and moderate to severe OHSS rate were significantly higher than those in the first GnRH an-tagonist cycle(P＜0.05).The GnRH antagonist protocol group also showed similar improvements.③ The com-parison of the second COH cycle between two groups showed that the total number of Gn days,total Gn usage,and total Gn cost in the luteal phase long protocol group were significantly higher(P＜0.05),while the E2 and LH on the day of hCG injection,and the maturation rate of eggs were significantly lower than those in the GnRH antagonist protocol group(P＜0.05).However,there was no statistically significant difference in the number of retrieved eggs,2PN fertilization,2PN cleavage,blastocyst formation rate,high-quality blastocyst formation rate,and OHSS rate between the two groups;④ The comparison of fresh transplantation cycles for the second COH cycle between the two groups showed that the luteal phase long protocol fresh transplantation rate,implantation rate,clinical preg-nancy rate,and live birth rate were slightly higher than those of the GnRH antagonist protocol group,but the differ-ence was not statistically significant.Comparing the outcomes of pregnancy following the initial frozen-thawed em-bryo transfer(FET)between two groups,the biochemical pregnancy rate and clinical pregnancy rate of the GnRH antagonist protocol group were higher than those of the luteal phase long protocol group(P＜0.05).However,no significant statistical variations were found in implantation rate,live birth rate,neonatal gestational age,and birth weight.Conclusion For PCOS patients who fail the first GnRH antagonist protocol,an appropriate increase in the initiating dose and usage of Gn can achieve satisfactory pregnancy outcomes with both protocols.Compared with change to a luteal phase long protocol,reusing the GnRH antagonist protocol still maintains its long-standing advan-tages,such as shorter total Gn days,lower costs,and better patient compliance.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Objective To explore the therapeutic mechanism of compound Yuye Decoction against diabetic cardiomyopathy(DCM).Methods Drugbank,Gene Cards,OMIM and PharmGKb databases were used to obtain DCM-related targets,and the core targets were identified and functionally annotated by protein-protein interaction network analysis followed by GO and KEGG enrichment analysis.The"Traditional Chinese Medicine-Key Component-Key Target-Key Pathway"network was constructed using Cytoscape 3.9.1,and molecular docking was carried out for the key components and the core targets.In the animal experiment,Wistar rat models of DCM were treated with normal saline or Yuye Decoction by gavage at low(0.29 g/kg)and high(1.15 g/kg)doses for 8 weeks,and the changes in cardiac electrophysiology and histopathology were evaluated.The changes in serum levels of LDH,CK,and CK-MB were examined,and myocardial expressions of PI3K,P-PI3K,Akt,P-AKT,BAX,IL-6,and TNF-α were detected using Western blotting.Results We identified 61 active compounds in Yuye Decoction with 1057 targets,3682 DCM-related disease targets,and 551 common targets between them.Enrichment of the core targets suggested that apoptosis,inflammation and the PI3K/Akt pathways were the key signaling pathways for DCM treatment.Molecular docking studies showed that the active components in Yuye Decoction including gold amidohydroxyethyl ester and kaempferol had strong binding activities with AKT1 and PIK3R1.In DCM rat models,treatment with Yuye Decoction significantly alleviated myocardial pathologies,reduced serum levels of LDH,CK and CK-MB,lowered myocardial expressions of BAX,IL-6 and TNF-α,and increased the expressions of P-PI3K and P-AKT.Conclusion The therapeutic effect of compound Yuye Decoction against DCM is mediated by its multiple active components that act on multiple targets and pathways to inhibit cardiomyocyte apoptosis and inflammatory response by regulating the PI3K/Akt signaling pathway.

Objective The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization(IVF)processes using gonadotrophin-releasing hormone(GnRH)antagonist protocol,GnRH agonist long protocol,and early follicular phase protocol.We aim to provide reliable reference for future clinical treatments.Methods We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023.1)In the overall patient population,we comprehensively compared the basic characteristics,the embryo development,and the clinical outcomes of patients treated with three different ovarian stimulation protocols,including the GnRH antagonist protocol group(n=4 173),the agonist long protocol group(n=2 410),and the early follicular phase long protocol group(n=341).2)We divided the overall population into three age groups,one group for patients under 30 years old(n=2 576),one for patients aged 30-35(n=3 249),and one for patients older than 35 years old(n=1 099).Then,we compared the three stimulation protocols based on the group division.We separately compared the embryo development and clinical outcomes of patients using the three stimulation protocols in the under 30 years old,the 30-35 years old,and the over 35 years old age groups.With this analysis,we aimed to explore the response of different age groups to different stimulation protocols and their impact on the success rate of IVF.Results 1)In the overall population,we found that the average number of oocytes retrieved in the GnRH agonist long protocol group was significantly higher than that in the GnRH antagonist protocol group([13.85±7.162]vs.[13.36±7.862],P=0.022 4),as well as the early follicular phase long protocol group([13.85±7.162]vs.[11.86±6.802],P<0.000 1).Patients in the GnRH antagonist protocol group not only had a significantly lower starting dose of gonadotrophin(Gn)compared to the other two groups(P<0.05)but also had a significantly lower number of days of Gn use(P<0.05).The blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(64.91% vs.62.35%,P<0.000 1)and the early follicular phase long protocol group(64.91% vs.61.18%,P=0.000 1).However,there were no significant differences in the clinical pregnancy rates or the live birth rates among the three groups treated with different ovarian stimulation protocols(P>0.05).2)In the<30 age group,the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(66.12% vs.63.33%,P<0.000 1)and the early follicular phase long protocol group(66.12% vs.62.13%,P=0.009 4).In the 30-35 age group,the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups,significantly higher compared to the GnRH agonist long protocol group(64.88% vs.62.93%,P=0.000 9)and the early follicular phase long protocol group(64.88% vs.60.39%,P=0.001 1).In the>35 age group,the blastocyst formation rate in the GnRH antagonist protocol group was significantly higher than that in the GnRH agonist long protocol group(59.83% vs.56.51%,P=0.009 3),while there was no significant difference compared to that of the early follicular phase long protocol group(P>0.05).In the three age groups,we found that there were no significant differences in clinical pregnancy rate,live birth rate,and neonatal outcome indicators(fetal weight and Apgar score)among the three stimulation protocols(antagonist protocol,GnRH agonist long protocol,and early follicular phase long protocol)(P>0.05).The findings showed no significant differences between clinical and neonatal outcomes in patients of all ages,regardless of the ovarian stimulation protocol,suggesting that the three ovarian stimulation protocols have similar therapeutic effects in patients of different ages.The results of this study have important implications for the selection of an appropriate ovarian stimulation protocol and the prediction of treatment outcomes.Conclusion In the younger than 30 and 30-35 age groups,the GnRH antagonist protocol showed a more significant advantage over the GnRH agonist long protocol and the early follicular phase long protocol.This suggests that for younger and middle-aged patients,the antagonist protocol may lead to better outcomes during ovarian stimulation.In the older than 35 age group,while the antagonist protocol still outperformed the GnRH agonist long protocol,there was no significant difference compared to the early follicular phase long protocol.This may imply that with increasing age,the early follicular phase long protocol may have effects similar to the antagonist protocol to some extent.The advantages of the antagonist protocol lie in its ability to reduce stimulation duration and the dosage of GnRH,while enhancing patient compliance with treatment.This means that patients may find it easier to accept and adhere to this treatment protocol,thereby improving treatment success rates.Particularly for older patients,the use of the antagonist protocol may significantly increase the blastocyst formation rate,which is crucial for improving the success rates.Although there were no significant differences in the clinical outcomes of patients treated with the three protocols in each age group,further research is still needed to validate these findings.Future multicenter studies and increased sample sizes may help comprehensively assess the efficacy of different stimulation protocols.Additionally,prospective studies are needed to further validate these findings and determine the optimal treatment strategies.