Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B （NF-κB） in co-cultured peripheral blood mononuclear cells （PBMCs） and human fibroblast-like synoviocytes （FLSs） from patients with ankylosing spondylitis （AS）. MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs， and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs， while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells（6.48 g·kg^-1）. To investigate the effect of HQC-containing serum on the viability of co-cultured cells， and the experiment was divided into the following groups based on the dilution concentration： blank group， 10% HQC group， 20% HQC group， and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group， the experiment was divided into three groups： normal group， model group， and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid， the experiment was divided into the following groups： blank group， si-NC group （with transfection reagent）， si-circ_0001543-1 group （with transfection reagent and interference plasmid No. 1 targeting circ_0001543）， si-circ_0001543-2 group （with transfection reagent and interference plasmid No. 2 targeting circ_0001543）， and si-circ_0001543-3 group （with transfection reagent and interference plasmid No. 3 targeting circ_0001543）.For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid， the experiment was divided into the following groups： blank group， OE-NC group （with transfection reagent）， and OE-circ_0001543 group （with transfection reagent and overexpression plasmid targeting circ_0001543）.To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group， the experiment was divided into the following groups： si-NC group， si-CircRNA_0001543 group， OE-NC group， and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， IL-10， IL-37， and tumor necrosis factor-α （TNF-α）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure the expression of CircRNA_0001543， IκBα， and NF-κB p65. ResultsAfter 48 hours， 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs， which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the model group were significantly increased （P<0.01）， while the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly decreased （P<0.01）. Compared with those in the model group， the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased （P<0.05）， and the expressions of CircRNA_0001543 mRNA， IL-10， and IL-37 were significantly increased （P<0.05）， with the most prominent changes in the 30% drug-containing serum group （P<0.01）. Compared with that in the si-NC group， the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group （P<0.01）. Compared with that in the OE-NC group， the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group （P<0.01）， indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules， si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α and decreased the expressions of IL-10 and IL-37 （P<0.01）. In contrast， OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA， IκBα mRNA， IL-1β， and TNF-α （P<0.01） and increased the expressions of IL-10 and IL-37 （P<0.01）. ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543， regulating the NF-κB pathway， suppressing pro-inflammatory cytokines， and enhancing anti-inflammatory cytokine expression.

Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension，clinical characteristics， and traditional Chinese medicine（TCM） syndromes in patients with hepatolenticular degeneration ［also known as Wilson disease（WD）］. MethodsA total of 104 patients with WD accompanied by abnormal muscle tension（increased or decreased，hereinafter the same） who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected，all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension，Goldstein， and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed，and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzed ResultsAmong the 104 patients with WD ，the phlegm and stasis syndrome was the most common（60 patients），followed by the damp-heat syndrome（33 patients），and the least common was the liver-kidney Yin deficiency syndrome（11 patients）. The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group（P<0.01）. The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group（P<0.05），and the F value of the lower limbs of each group was higher than that of the upper limbs（P<0.01）. Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group（P<0.05）. There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs（r=0.20，P<0.05，r=0.38，P<0.01）and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores（muscle tension of the upper limbs in the phlegm and stasis syndrome group，r=0.36，P<0.01，r=0.42，P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group，r=0.70，P<0.01，r=0.60，P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group，r=0.64，P<0.01，r=0.53，P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group，r=0.59，P<0.01，r=0.70，P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group，r=0.70，P<0.01，r=0.74，P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group，r=0.85，P<0.01，r=0.62，P<0.01）. Conlusion： The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome