OBJECTIVE To observe the clinical efficacy of Yangyin Yifei Decoction in treating type 2 diabetes mellitus(T2DM)patients with of qi-yin deficiency and elevated serum keratin 19 fragment(Cyfra21-1).METHODS Sixty patients with T2DM of qi-yin deficiency type and elevated serum Cyfra21-1 who met the inclusion criteria were selected and randomly divided into an observation group and a control group,30 cases in each group.The control group was given oral hypoglycemic treatment with metformin hydrochlo-ride sustained-release tablets and dapagliflozin tablets,and the observation group was given Yangyin Yifei Decoction on the basis of the treatment of the control group.The treatment course of both groups was 12 weeks.Before and after treatment,the changes of traditional Chinese medicine(TCM)syndrome scores,fasting blood glucose(FBG)and 2-hour postprandial glucose(2 h PG),glycosylated he-moglobin(HbAlc),serum Cyfra21-1 and Cyfra21-1 specific T cell response,triglycerides(TG),total cholesterol(TC),alanine ami-notransferase(ALT),aspartate aminotransferase(AST),urea(UR),and creatinine(CREA)were observed in the two groups.RE-SULTS After treatment,FBG,2 h PG,HbAlc,and TCM syndrome scores of the two groups of patients decreased significantly(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);TG and TC in the observation group were significantly reduced(P<0.01),serum Cyfra21-1 was significantly decreased(P<0.01),and Cyfra21-1-specific T cells in PBMCs were significantly increased(P<0.01),which was better than the control group(P<0.01);there was no significant change in liver and kidney function in the two groups.CONCLUSION Yangyin Yifei Decoction combined with basic hypoglycemic regimen can significantly improve blood glucose and lipid metabolism in T2DM patients with qi-yin deficiency and elevated serum Cyfra21-1,enhance the function of Cyfra21-1-specific T cells,and improve the body's immunity,with high safety.

Objective:To analyze the significance of ultrasound super microvascular imaging (SMI) combined with strain ratio (SR) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 110 patients with breast masses (110 lesions) admitted to Jiande Branch of the Second Affiliated Hospital of Zhejiang University from October 2022 to November 2024 were retrospectively selected, including 65 benign masses (benign group) and 45 malignant masses (malignant group). Both groups received SMI and strain elastography (SE) examination. The clinical and ultrasonic parameters SMI blood flow signal grade, vascular index (VI), global SR (ESR), local SR (LSR) and other indicators of the two groups were compared, and the independent risk of breast tumor malignancy was screened by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of SMI blood flow signal grading, VI and ESR combined detection in the differential diagnosis of breast tumor malignancy.Results:The proportion of irregular shape, unclear boundary, microcalcification, convergence sign and angulation sign in the malignant group were higher than those in the benign group: 80.00%(36/45) vs. 55.38%(36/65), 57.78%(26/45) vs. 33.85%(22/65), 44.44%(20/45) vs. 13.85%(9/65), 55.56%(25/45) vs. 9.23%(6/65), 60.00%(27/45) vs. 15.38%(10/65), there were statistical differences ( P<0.05). The SMI blood flow signal grade in the malignant group was higher than that in the benign group, the VI, ESR and LSR in the malignant group were higher than those in the benign group: (6.53 ± 0.68)% vs. (3.14 ± 0.36)%, 4.62 ± 0.48 vs. 2.53 ± 0.27, 31.45 ± 3.29 vs. 20.16 ± 2.35, there were statistical differences ( P<0.05). Logistic regression analysis showed that irregular shape, unclear boundary, microcalcification, SMI blood flow signal grade, VI and ESR were independent risk factors for malignant breast mass ( P<0.05). ROC curve analysis results showed that the sensitivity, specificity and accuracy of SMI blood flow signal classification, VI and ESR combined in predicting breast tumor malignancy were 84.26%, 83.17% and 87.65%, respectively, and the area under the curve was 0.896, which were higher than the results predicted by each index alone. Conclusions:There are certain characteristic changes of SMI in benign and malignant breast masses. SMI combined with SR has good value in differential diagnosis of benign and malignant breast masses.

Objective This study aimed to investigate the efficacy of modified endoscopic autologous cartilage eustachian tube pharyngeal orifice tuboplasty(MEACETT)in patients with patulous eustachian tube(PET).Meth-ods A retrospective analysis was conducted on the clinical data of 27 patients(30 ears)diagnosed with PET who underwent MEACETT.Autologous cartilage was used through the incision at the posterior end of the inferior turbi-nate and filled into the lateral wall of the pharyngeal orifice of the eustachian tube.Without affecting the movement function of the eustachian tube during swallowing,the collapse of the pharyngeal orifice was fully filled.Before and after the surgery,the visual analogue scale(VAS),the eustachian tube dysfunction questionnaire-7(ETDQ-7)and hospital anxiety and depression scale(HADS)was used for assessment to evaluate the surgical efficacy.Results There was no significant difference in depression scores before and after surgery(P＞0.05).However,postopera-tive anxiety scores,ETDQ-7 scores,and VAS scores were significantly lower than preoperative scores(P＜0.05).Among the 27 patients,9 showed significant symptom relief,13 exhibited partial relief,and 5 had no significant change compared to preoperative symptoms.The overall response rate of the treatment(significant relief and partial relief)was 81.48％(22/27).All surgeries were successfully performed.Except for secretory otitis media occurring in 2 cases,no major complications were observed.Conclusion MEACETT demonstrates significant symptom relief in PET patients,with high surgical safety and low complication rates,making it worthy of clinical promotion.

Objective To evaluate the diagnostic efficacy of the R value in tubomanometry(TMM)for the di-agnosis of patulous eustachian tube(PET).Methods The clinical data of 58 patients with PET and 65 controls were retrospectively analyzed.TMM was performed on both groups under nasopharyngeal pressures of 30,40,and 50 mbar respectively.The diagnostic efficacy of the R value for PET was evaluated through receiver operating char-acteristic(ROC)curves.Results In the control group,the average R values under nasopharyngeal pressures of 30,40,and 50 mbar were 0.86±0.50,0.76±0.41,and 0.68±0.34 respectively.In contrast,the corresponding R values in the PET group were significantly lower,which were 0.56±0.38,0.50±0.36,and 0.46±0.38 respec-tively.According to the ROC curve analysis,the areas under the curve(AUC)at these pressures were 0.62,0.74,and 0.74 respectively.The specificity and sensitivity of the R value under nasopharyngeal pressures of 30,40,and 50 mbar were 76.90％and 54.30％,74.60％and 68.10％,86.90％and 54.30％,respectively.Under pressures of 30,40,and 50 mbar,the incidence rates of R＞1 in the control group and the PET group were 29.23％(38/130)and 12.77％(12/94)(x2=8.69,P=0.003),20.00％(26/130)and 6.38％(6/94)(x2=7.20,P=0.007),10.00％(13/130)and 3.19％(3/94)(x2=2.87,P=0.09)respectively.Conclusion Although the low R value in TMM reflects the presence of PET to some extent,it does not provide adequate sensitivity and specificity to serve as an independent diagnostic criterion for PET.

Objective To establish the UPLC fingerprint of 10 batches of Gongliuning capsule and the content determination methods of 10 main components;To conduct network pharmacological research;To provide scientific basis for predicting the quality marker of Gongliuning capsule.Methods UPLC-DAD technique was used to establish the fingerprint of different batches of Gongliuning capsule samples and obtain the complete chemical composition information of Gongliuning capsule.With the help of network pharmacological research techniques,the target of chemical components of Gongliuning capsule and related pathways screened from various databases were predicted and analyzed,and the protein interaction network and composition-target-pathway diagram were constructed to predict the effective components of Gongliuning capsule.Based on the obtained pharmacodynamic substances,the content determination method of Gongliuning capsule was established to evaluate the quality of Gongliuning capsule.Results The fingerprints of Gongliuning capsule identified 17 common peaks.Combined with network pharmacology method,the candidate chemical components were analyzed,10 core targets and 42 metabolic pathways were obtained.Based on the testability of components and the availability of reference substances,10 compounds with high contribution were selected for content determination.Methodological verification results showed that all the 10 compounds had good linear relationship(r2>0.999 4)in the detection range,with good precision,accuracy and stability.Conclusion The established UPLC fingerprint,network pharmacology and multiple component content determination methods are highly specific,accurate and reliable.Combined with chemical pattern recognition,they can be effectively used for quality control and quality marker prediction of Gongliuning capsules.

OBJECTIVE To observe the clinical efficacy of Yangyin Yifei Decoction in treating type 2 diabetes mellitus(T2DM)patients with of qi-yin deficiency and elevated serum keratin 19 fragment(Cyfra21-1).METHODS Sixty patients with T2DM of qi-yin deficiency type and elevated serum Cyfra21-1 who met the inclusion criteria were selected and randomly divided into an observation group and a control group,30 cases in each group.The control group was given oral hypoglycemic treatment with metformin hydrochlo-ride sustained-release tablets and dapagliflozin tablets,and the observation group was given Yangyin Yifei Decoction on the basis of the treatment of the control group.The treatment course of both groups was 12 weeks.Before and after treatment,the changes of traditional Chinese medicine(TCM)syndrome scores,fasting blood glucose(FBG)and 2-hour postprandial glucose(2 h PG),glycosylated he-moglobin(HbAlc),serum Cyfra21-1 and Cyfra21-1 specific T cell response,triglycerides(TG),total cholesterol(TC),alanine ami-notransferase(ALT),aspartate aminotransferase(AST),urea(UR),and creatinine(CREA)were observed in the two groups.RE-SULTS After treatment,FBG,2 h PG,HbAlc,and TCM syndrome scores of the two groups of patients decreased significantly(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);TG and TC in the observation group were significantly reduced(P<0.01),serum Cyfra21-1 was significantly decreased(P<0.01),and Cyfra21-1-specific T cells in PBMCs were significantly increased(P<0.01),which was better than the control group(P<0.01);there was no significant change in liver and kidney function in the two groups.CONCLUSION Yangyin Yifei Decoction combined with basic hypoglycemic regimen can significantly improve blood glucose and lipid metabolism in T2DM patients with qi-yin deficiency and elevated serum Cyfra21-1,enhance the function of Cyfra21-1-specific T cells,and improve the body's immunity,with high safety.

Objective To establish the UPLC fingerprint of 10 batches of Gongliuning capsule and the content determination methods of 10 main components;To conduct network pharmacological research;To provide scientific basis for predicting the quality marker of Gongliuning capsule.Methods UPLC-DAD technique was used to establish the fingerprint of different batches of Gongliuning capsule samples and obtain the complete chemical composition information of Gongliuning capsule.With the help of network pharmacological research techniques,the target of chemical components of Gongliuning capsule and related pathways screened from various databases were predicted and analyzed,and the protein interaction network and composition-target-pathway diagram were constructed to predict the effective components of Gongliuning capsule.Based on the obtained pharmacodynamic substances,the content determination method of Gongliuning capsule was established to evaluate the quality of Gongliuning capsule.Results The fingerprints of Gongliuning capsule identified 17 common peaks.Combined with network pharmacology method,the candidate chemical components were analyzed,10 core targets and 42 metabolic pathways were obtained.Based on the testability of components and the availability of reference substances,10 compounds with high contribution were selected for content determination.Methodological verification results showed that all the 10 compounds had good linear relationship(r2>0.999 4)in the detection range,with good precision,accuracy and stability.Conclusion The established UPLC fingerprint,network pharmacology and multiple component content determination methods are highly specific,accurate and reliable.Combined with chemical pattern recognition,they can be effectively used for quality control and quality marker prediction of Gongliuning capsules.

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation