ObjectiveTo evaluate the effect of Ningying Formula （宁瘿方） combined with low-dose antithyroid drugs （ATDs） on the relapse risk for patients with Graves' hyperthyroidism （GH） during the remission phase， and to analyze the related factors between GH relapse and thyrotropin receptor antibody （TRAb） negativity， so as to provide evidence for the standardized management of GH in remission stage. MethodsA single-center retrospective cohort study was conducted， including 269 GH patients in the remission stage. After propensity score matching （PSM）， 102 matched pairs （204 patients） were established. The control group received low-dose ATDs as maintenance therapy， while the exposure group received the core Ningying Formula in addition to low-dose ATDs. The primary outcome was the GH recurrence rate； the secondary outcome was the thyrotropin receptor antibody （TRAb） negativity rate （TRAb＜1.75 IU/L）. Safety outcomes included treatment-related adverse events. Differences between groups were assessed using Cox regression models and Kaplan-Meier curves， with sensitivity analysis performed using inverse probability of treatment weighting （IPTW）. ResultsThe median follow-up in the matched cohort was 28.07 months. Regarding the GH recurrence outcome， the recurrence rate in the exposure group （18/102， 17.6%） was significantly lower than that in the control group （31/102， 30.4%； χ²=4.539， P=0.033）； regarding the TRAb negativity outcome， the TRAb negativity rate in the exposure group （50/102， 49.0%） was significantly higher than that in the control group （23/102， 22.5%； χ²=15.551， P＜0.001）. Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence ［HR=0.324， 95%CI（0.170， 0.617）， P＜0.001］. Male ［HR=2.209， 95%CI（1.079， 4.520）， P=0.030］， higher initial TRAb level ［per 1 IU/L increase： HR=1.033， 95%CI（1.003， 1.064）， P=0.032］， and larger thyroid volume ［per 1 ml increase： HR=1.045， 95%CI（1.003， 1.088）， P=0.035］ were identified as independent risk factors for recurrence； multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity ［HR=1.826， 95%CI（1.091， 3.056）， P=0.022］， while a higher initial TRAb level was associated with a lower probability of negativity ［HR=0.974， 95%CI（0.950， 0.998）， P=0.032］. Survival analysis showed significant differences in relapse rate between groups （Log-Rank P=0.003） and in TRAb outcomes （Log-Rank P=0.034）. The incidence of treatment-related adverse events was similar between groups （P=0.757）. The IPTW sensitivity analysis was consistent with the primary analysis， indicating robust results. ConclusionThe Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage， without increasing common adverse events， making it an optional strategy for reducing relapse risk during remission. Male gender， higher baseline TRAb level， and larger thyroid volume indicate a higher risk of recurrence， warranting focused follow-up and stratified management.

ObjectiveTo explore the improving effect of Huangqi Chifengtang（HCT） on atherosclerosis（AS）， and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase（AMPK）/peroxisome proliferator-activated receptor α（PPARα） signaling pathway and nucleotide-binding oligomerization domain（NOD）-like receptor thermal protein domain associated protein 3（NLRP3） inflammasome. MethodsEight C57BL/6J mice were set as the normal group， and 32 ApoE^-/- mice were randomly divided into the model group， the positive drug group（atorvastatin， 5 mg·kg^-1·d^-1）， HCT low- and high-dose groups（1.95， 3.90 g·kg^-1·d^-1）. ApoE^-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling， they were orally administered corresponding dose of drugs for 28 days， while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin（HE） staining was used to observe the pathological status of the aorta and liver in mice， Biochemical testing and enzyme-linked immunosorbent assay（ELISA） were used to detect the levels of total cholesterol（TC）， triglycerides（TG）， low-density lipoprotein cholesterol（LDL-C）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， C-reactive protein（CRP）， interleukin（IL）-1β， IL-18 in the serum， as well as superoxide dismutase（SOD）， malondialdehyde（MDA）， and reduced glutathione（GSH） in the liver. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to measure the mRNA expression levels of NLRP3， apoptosis-associated speck-like protein（ASC）， cysteinyl aspartate specific proteinase-1（Caspase-1）， Toll-like receptor 4（TLR4） in the aorta， and fatty acid synthase（FAS）， stearoyl-CoA desaturase 1（SCD1）， PPARα， and carnitine palmitoyltransferase 1A（CPT1A） in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3， Caspase-1， and ASC in the aorta， and Western blot was used to measure the protein expressions of AMPK， p-AMPK， sterol regulatory element binding protein-1c（SREBP-1c）， CPT1A， and FAS in the liver. ResultsCompared with the normal group， the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver， the levels of TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum were significantly increased（P<0.01）， and the mRNA and protein expressions of aortic TLR4， NLRP3， Caspase-1 and ASC were significantly upregulated（P<0.01）. The levels of SOD and GSH in the liver were significantly reduced， while the level of MDA was significantly increased（P<0.01）. The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated， while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced， while the expressions of SREBP-1c and FAS proteins were significantly increased（P<0.01）. Compared with the model group， the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC， LDL-C， AST， IL-1β and IL-18 in the serum of the low-dose HCT group， as well as TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum of the high-dose HCT group， were significantly reduced（P<0.01）. The mRNA expressions of TLR4， NLRP3 and Caspase-1 in the aorta of the low-dose HCT group， as well as TLR4， NLRP3， Caspase-1 and ASC in the aorta of the high-dose HCT group， were significantly downregulated（P<0.01）. The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group， as well as NLRP3， Caspase-1 and ASC in the high-dose HCT group， were significantly downregulated（P<0.01）. The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased， while the level of MDA in the high-dose HCT group was significantly decreased（P<0.05， P<0.01）. In the HCT-treated group， the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated， while the mRNA expressions of PPARα and CPT1A were significantly downregulated， the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased， while the protein expressions of SREBP-1c and FAS were significantly decreased（P<0.05， P<0.01）. ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses， thereby reducing hepatic lipid deposition and AS plaque formation.

Objective:This study aimed to evaluate the therapeutic effect of intratympanic injection of ganglioside in patients with refractory sudden deafness. Methods:A total of 120 patients with sudden deafness, aged 18-65 years, whose onset was within 11-42 days, failed to respond to conventional treatment, and had an average hearing threshold（500-4 000 Hz）>60 dB were selected. They were prospectively and randomly divided into a control group of 61 cases and an experimental group of 59 cases. The control group was treated according to the recommended protocol of the Chinese Medical Association（postauricular injection of methylprednisolone）, while the experimental group was treated with intratympanic injection of monosialotetrahexosylganglioside sodium+postauricular injection of methylprednisolone. Both groups were simultaneously administered oral ginkgo biloba extract and citicoline tablets. Hearing was re-examined two weeks after the completion of treatment, and the therapeutic effects of the two different treatment methods were compared and analyzed. Results:The effective rate was 29.51% in the control group and 54.24% in the experimental group（P<0.01）. The average hearing threshold improved by 11.57 dB HL in the control group and 22.50 dB HL in the experimental group（P<0.05）. Conclusion:The combination of postauricular injection of methylprednisolone and intratympanic injection of ganglioside is more effective than postauricular injection of methylprednisolone alone in the treatment of refractory sudden deafness. The earlier the treatment, the better the therapeutic effect.
Humans ; Middle Aged ; Hearing Loss, Sudden/drug therapy* ; Adult ; Prospective Studies ; Young Adult ; Aged ; Adolescent ; Male ; Female ; Injection, Intratympanic ; Gangliosides/administration & dosage* ; Methylprednisolone/therapeutic use* ; Treatment Outcome

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

OBJECTIVE To explore the short-term efficacy,safety and related influencing factors of subcutaneous immunotherapy(SCIT)in children with allergic rhinitis(AR).METHODS Retrospective analyzed the clinical data of 147 children with AR who underwent SCIT at Shenzhen Hospital of Southern Medical University from August 2020 to May 2024.The clinical characteristics and laboratory parameters were collected,the visual analogue scale(VAS),total symptom score(TSS),total medication score(TMS)and combined symptom medication score(CSMS)were compared at the baseline and 3,6 and 12 months after treatment.The incidence of local adverse reactions(LRs)and systemic adverse reactions(SRs)during treatment was also documented.RESULTS A total of 147 children with AR aged 5-18 years were included in the study.A significant reduction was observed in VAS,TSS,TMS and CSMS at months 3,6 and 12 of follow up compared with baseline(all P<0.001),and the short-term onset time was months 3 after treatment.The level of VitD3 in the effective group was significantly higher than that in the ineffective group(P<0.001).Serum VitD3 level was negatively correlated with clinical symptom(R=-0.3,P=0.026).The total number of injections in 147 children was 3201.LRs occurred in 52 children(35.4％),the number of injections was 69(2.2％).SRs occurred in 21 children(14.3％),and the number of injections was 34(1.1％).No grade Ⅲ or Ⅳ SRs occurred.In the logistic regression analysis,body mass index(BMI)was a risk factor for LRs(OR:2.220,95％CI:1.009-4.887,P=0.048).CONCLUSION SCIT demonstrates significant early efficacy and a favorable safety profile safety in children with AR.Serum Vitamin D3 deficiency can affect the short-term efficacy of SCIT.Overweight and obese children are prone to develop local adverse reactions.

Objective To investigate the status and influencing factors of type 2 diabetes mellitus(T2DM)patients' fear of complications,and to provide a reference for formulating targeted intervention measures.Methods From April to November 2024,370 patients with T2DM in 2 tertiary general hospitals in Daqing City were selected by convenience sampling method.General data questionnaire,Fear of Complications Questionnaire,Self-Perceived Burden Scale,Psychological Capital Questionnaire,Mishel Uncertainty in Illness Scale and Family Apgar Index Questionnaire were used for investigation.Univariate analysis and binary Logistic regression were performed to analyze the influencing factors.Results A total of 364 valid questionnaires were collected,with an effective recovery rate of 98.38％.The score of Fear of Complications Questionnaire was(23.47±7.47),and the incidence of fear of complications was 22.25％.Logistic regression analysis showed that medical payment methods,the number of complications,positive psychological capital and family care were the influencing factors of FoC in T2DM patients.Conclusion The fear of complications in T2DM patients is at a moderate level.Nursing staff should pay attention to the early assessment of patients' fear of complications,promptly identify and take effective measures to reduce the level of patients' fear of complications,improve their quality of life.

[Purpose]To analyze the incidence and mortality of pancreatic cancer in 2020 and the change trend from 2010 to 2020 in cancer registration areas of Gansu Province.[Methods]The data of pancreatic cancer from 2010 to 2020 were collected from cancer registries in Gansu Province.The crude incidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate and proportion of pancreatic cancer were calculated.Joinpoint 4.7.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC of pancreatic cancer in cancer registration areas of Gansu Province from 2010 to 2020.[Results]In 2020,a total of 838 new cases of pancreatic cancer were reported in the cancer registration areas of Gansu Province,with a crude incidence rate of 6.52/105,ASIRC and ASIRW of 4.03/105 and 4.49/105 respectively,accounting for 2.50％of all malignant tumor incidence.In 2020,702 cases of pan-creatic cancer deaths were reported in the cancer registration areas of Gansu Province,with a crude mortality rate of 5.46/105,ASMRC and ASMRW of 3.25/105 and 3.73/105,respectively,ac-counting for 3.98％of all malignant tumor deaths.From 2010 to 2020,a total of 2 413 cases of pancreatic cancer were reported in cancer registration areas in Gansu Province,accounting for 1.90％of all malignant tumors in the province.The crude incidence rate of pancreatic cancer was 5.28/105,the ASIRC was 4.18/105,the ASIRW was 4.63/105,and the cumulative rate of 0～74 years old was 0.49％.From 2010 to 2020,a total of 1 871 pancreatic cancer deaths were reported in cancer registration areas of Gansu Province,accounting for 2.38％of all malignant tumor deaths in the province.The crude mortality rate was 3.92/105,the ASMRC was 3.09/105,the ASMRW was 3.50/105,and the cumulative rate of 0～74 years old was 0.36％.In terms of sex and region,the incidence and mortality of pancreatic cancer from 2010 to 2020 in men were higher than those in women,and higher in rural areas than those in urban areas.From 2010 to 2020,the incidence and mortality were at a low level under the age of 44 years old,and increased significantly after 45 years old,reaching a peak in the age group of 80～84 years old.ASIRC showed no significant change from 2010 to 2020 with an AAPC of 0.41 1％(P＞0.05).From 2010 to 2020,the ASMRC showed an significantly increasing trend with an AAPC of 6.515％(P=0.014).[Conclusion]From 2010 to 2020,the ASRIC of pancreatic cancer in Gansu Province showed no significant change,while the ASMRC showed a significantly in-creasing trend.The incidence and mortality rates were higher in men than those in women and higher in rural areas than those in urban areas.Middle-aged and elderly men in rural areas are the key groups of prevention and treatment of pancreatic cancer,so targeted prevention and control measures should be carried out.

Objective:To explore the value of dual-layer spectral CT virtual monoenergetic images (VMI) in contrast-enhanced abdominal CT scans with reduced contrast medium volume in pediatric tumor patients.Methods:The study is a self-matched case-control study. From January to October 2024, pediatric patients admitted to Shandong Cancer Hospital with abdominal tumors who underwent low contrast dose spectral CT contrast-enhanced scans during follow-up were prospectively included. A total of 47 patients aged (6.2±2.2) years (4-14 years) were enrolled. Usual contrast dose enhanced CT served as the conventional-dose group, while the follow-up low-dose spectral CT scans employed a protocol with half the contrast agent dose (low-dose group). Images were reconstructed as conventional CT images and VMI at 45, 55, and 65 keV. Using muscle as the reference background, differences in CT values and contrast-to-noise ratio (CNR) in the aorta, kidneys, liver, and spleen were compared between the low-dose group and conventional-dose group. Multi-group comparisons were performed using the Friedman test. Post-hoc pairwise comparisons were conducted with Bonferroni correction for P-values. Results:CT values and CNRs for all measured regions progressively increased with decreasing keV levels in spectral CT VMI. Significant overall differences were found in CT values and CNRs for the aorta, kidneys, liver, and spleen among the low-dose group (all VMIs) and the conventional-dose group (all P<0.001). At 65 keV VMI in the low-dose group, both CT values and CNRs (except for the liver CNR) were significantly lower than those in the conventional-dose group (all adjusted P<0.05). At 55 keV VMI in the low-dose group, CT values and CNRs for all regions did not show statistically significant differences compared to the conventional-dose group (all adjusted P>0.05). At 45 keV VMI in the low-dose group, CT values for all structures and CNR for the spleen were significantly higher than those in the conventional-dose group (all adjusted P<0.05). However, no statistically significant difference was found in CNRs for the aorta, kidneys, and liver (adjusted P=1.000, 0.313, and 0.503, respectively). Conclusion:When the contrast dose is halved, spectral CT 45 keV VMI enhances CT attenuation values and CNR in the abdomen of pediatric tumor patients, while 55 keV VMI provides image quality comparable to that of conventional-dose CT.

Chronic hepatitis B(CHB)is the main cause of hepatocellular carcinoma(HCC).Early prediction and diagnosis of HCC in CHB patients can further reduce the onset risk of HCC and improve patient prognosis.Scholars at home and abroad have proposed a number of HCC risk prediction models for CHB patients,and these models have achieved new development and opti-mization in the era of antiviral therapy.Due to differences in research backgrounds,these models vary in the use of antiviral drugs,included variables(such as host factors,viral activity,cirrhosis status,etc.)and application scenarios.At the same time,the application of artificial intelligence and liquid biopsy technology in risk prediction models has become a new research highlight.This paper aims to compare the HCC risk prediction models reported so far for CHB patients,clarify the characteristics of each model,explore appropriate HCC risk prediction methods,and provide reference for the risk prediction of hepatitis B virus related HCC.