The processing mechanism of the human brain for speech information is a significant source of inspiration for the study of speech enhancement technology. Attention and lateral inhibition are key mechanisms in auditory information processing that can selectively enhance specific information. Building on this, the study introduces a dual-branch U-Net that integrates lateral inhibition and feedback-driven attention mechanisms. Noisy speech signals input into the first branch of the U-Net led to the selective feedback of time-frequency units with high confidence. The generated activation layer gradients, in conjunction with the lateral inhibition mechanism, were utilized to calculate attention maps. These maps were then concatenated to the second branch of the U-Net, directing the network's focus and achieving selective enhancement of auditory speech signals. The evaluation of the speech enhancement effect was conducted by utilising five metrics, including perceptual evaluation of speech quality. This method was compared horizontally with five other methods: Wiener, SEGAN, PHASEN, Demucs and GRN. The experimental results demonstrated that the proposed method improved speech signal enhancement capabilities in various noise scenarios by 18% to 21% compared to the baseline network across multiple performance metrics. This improvement was particularly notable in low signal-to-noise ratio conditions, where the proposed method exhibited a significant performance advantage over other methods. The speech enhancement technique based on lateral inhibition and feedback-driven attention mechanisms holds significant potential in auditory speech enhancement, making it suitable for clinical practices related to artificial cochleae and hearing aids.
Humans ; Attention/physiology* ; Speech Perception/physiology* ; Neural Networks, Computer ; Speech ; Noise ; Feedback

ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills （FBRP） in the intervention of alcoholic liver disease （ALD） using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group， model group， and FBRP low-， medium-， and high-dose groups （9.6， 19.2， 38.4 mg·kg^-1）. Except for the normal group， the remaining groups were given 56° white wine by gavage to establish the acute ALD model， with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group， model group， and FBRP medium-dose group （19.2 mg·kg^-1）. The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin （HE）， Sirius Red， oil red O staining， and enzyme-linked immunosorbent assay （ELISA）. Intoxication behaviors of each group were objectively evaluated through sobering-up time， net-catching， and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue， with experimental validation by ELISA， Western blot， and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in liver tissues of mice in the acute and chronic ALD model groups were significantly increased （P<0.05）. Compared with the model group， the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased （P<0.05）. Compared with the normal group， the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks （P<0.01）. Compared with the model group， the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks （P<0.05）. Compared with the normal group， the expression of high mobility group protein B1 （HMGB1） protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased （P<0.01）. Compared with the model group， the expression of HMGB1 protein in FBRP medium dose group was significantly decreased （P<0.05，P<0.01）. Compared with the normal group， the expression of brain-derived neurotrophic factor （BDNF） protein and the release of γ-aminobutyric acid （GABA） in the prefrontal cortex of the model group were significantly decreased （P<0.01）. Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased （P<0.05）. ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.

ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups： control （pure water） and Ruyi Zhenbaowan （1.8 g·kg^-1）. The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h， the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C₁₈ column （2.1 mm × 150 mm， 1.7 μm） with a mixture of 0.1% formic acid aqueous solution （A） and acetonitrile （B） as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min，97%~80%A；15~30 min ，80%~60%A；30~40 min，60%~30%A；40~45 min，30%~5%A. The ion source was electrospray ionization， and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan， and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid， respectively. In addition， the fragmentation rules of apigenin， apigenin-7-O-glucuronide， galangin， liquiritin， piperine， glycyrrhizic acid， eugenol， gallic acid， and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo， providing theoretical support for exploring active substances and performing quality control.l.

Objective:To investigate the clinical characteristics and prognosis of pancreatic acinar cell carcinoma (PACC).Methods:A retrospective case-control study analysis was conducted on the clinical data of 15 PACC patients admitted to Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University from June 2010 to May 2023. The clinical features and prognosis were analyzed.Results:Among the 15 patients with PACC, there were 9 males and 6 females, with a median age of 56 years, age ranged from 34 to 78 years. Abdominal pain was the initial symptom in 80.0% (12/15) of patients. Only 3 patients had elevated serum alpha-fetoprotein or carbohydrate antigen 19-9 levels. 80.0% (12/15) of the tumors were located in the pancreatic head, with an mean maximum diameter was (5.85±3.27) cm. CT scans showed heterogeneous enhancement in all patients, with cystic changes observed in 10 patients′ tumors. 7 patients underwent surgical treatment, including 1 patient involving venous resection and 2 patients involving partial gastrectomy; postoperative staging revealed that stage IB in 3 patients, IIA in 3 patients, and stage Ⅲ in 1 patient. Immunohistochemistry showed that there were 5 cases of Syn (+ ), 3 cases of CgA (+ ), 2 cases of AFP (+ ), 7 cases of Trypsin (+ ), 2 cases of CK7 (+ ), 2 cases of CK19 (+ ), 7 cases of β-catenin (+ ) and 2 cases of CD56 (+ ). Treatment after surgery included adjuvant chemotherapy for all surgical patients. 4 patients received systemic therapy, while 4 patients did not receive any treatment. Follow-up was completed for 11 patients, and lost in 4 patients; among the 7 patients who underwent surgical resection, 3 patients died with an average survival time of 44 months, ranged from 24 to 74 months, while the remaining 4 patients were alive with an average follow-up time of 26 months, ranged from 14 to 38 months. Among the 4 patients treated with systemic therapy, the average survival time was 16 months, ranged from 2 to 41 months.Conclusions:PACC is a rare pancreatic tumor that mainly affects elderly men. Clinical symptoms are often atypical, and there are no specific serum markers. The characteristic imaging findings include uneven enhancement with cystic changes, and positivity for trypsin on immunohistochemistry. Surgical resection combined with adjuvant therapy can provide long-term survival for patients, while those with distant metastasis have a poorer prognosis.

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

Objective:To review our clinical experience on total pancreatectomy in treatment of pancreatic diseases.Methods:The clinical data of 25 patients with pancreatic diseases who underwent total pancreatectomy at Nanjing Drum Tower Hospital from February 2016 to October 2019 were retrospectively analyzed. The data on general information, surgical methods, postoperative complications, changes in postoperative pancreatic endocrine and exocrine functions and quality of life were analyzed.Results:There were 16 males and 9 females, aged (60.9±9.4) years. Planned selective surgery was carried out in 16 patients while unplanned operations in 9 patients. There were 15 patients with pancreatic neoplasms with 4 patients who received neoadjuvant or conversion therapy, 6 patients with intraductal papillary mucinous neoplasms, 3 patients with chronic pancreatitis and 1 patient with pancreatic neuroendocrine carcinoma. The total postoperative complication rate was 36% (9/25). One patient died in the perioperative period, and one patient underwent a second operation. After 6 months of operation, 2 of 24 patients had died. The remaining patients had a fasting blood sugar of (8.9±1.6) mmol/L, with an insulin dosage of (30.7±10.6) U/d. The average dosage of trypsin was (1.1±0.3) g/d. The quality of life score reached or exceeded the preoperative levels.Conclusions:Total pancreatectomy was safe and feasible for some pancreatic diseases. For patients with pancreatic cancer, its long-term oncological outcomes need further studies.

Objective:To identify the risk factors of clinically relevant pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) for Vater′s ampullary carcinoma.Methods:The clinical data of 93 Vater's ampullary carcinoma patients who had undergone PD in Nanjing Drum Tower Hospital from January 2018 to December 2020 was retrospectively analyzed. According to the occurrence of CR-POPF, all patients were divided into the CR-POPF group and no CR-POPF group. Univariate analysis and multivariate analysis by logistic regression model were performed for perioperative risk factors of CR-POPF to identify the independent risk factors for CR-POPF after PD for Vater's ampullary carcinoma.Results:44 patients developed CR-POPF and the rate of CR-POPF was 47.3%(44/93). The most frequently detected microorganisms from abdominal drain fluid after operation were Klebsiella pneumoniae (25.8%), Enterococcus faecalis (19.4%), Enterobacter cloacae (11.8%) and Enterococcus faecium (10.7%). The results of univariate analysis showed that operation time, C-reactive protein (CRP) on postoperative day (POD)1, Klebsiella pneumoniae, Enterococcus faecalis and Enterococcus faecium in the abdominal drainage were statistically different between the two groups (all P value <0.05). Multivariate analysis revealed that CRP on POD1 ( OR 1.029, 95% CI 1.003-1.055, P=0.026), Klebsiella pneumoniae( OR 8.671, 95% CI 2.366-31.772, P=0.001), Enterococcus faecalis( OR 10.497, 95% CI 2.306-41.776, P=0.002) and Enterococcus faecium ( OR 22.580, 95% CI 2.303-221.403, P=0.007) in the abdominal drainage were independent risk factors for the development of CR-POPF after PD for Vater′s ampullary carcinoma. Conclusions:CRP on POD1, Klebsiella pneumoniae, Enterococcus faecalis and Enterococcus faecium in the drain samples were independent risk factors for the development of CR-POPF after PD for Vater′s ampullary carcinoma.

【Objective】 To investigate the feelings of blood donors during blood donation and its influencing factors, thus providing references for high quality blood donation service for blood banks. 【Methods】 A self-developed questionnaire concerning voluntary blood donation was randomly issued by the research group and recruited investigators among blood donors in 6 street blood donation sites of Nanjing Red Cross Blood Center at weekends during December 1~23, 2018. The basic information of blood donors, the difference of feelings during blood donation and the influencing factors were analyzed by descriptive analysis, chi-square test and binary Logistic regression analysis, respectively. 【Results】 A total of 405 questionnaires were issued, and all 405 copies were valid, with the response rate at 100% (405/405). Among the valid questionnaires, 46.67% (189/405) were first-time blood donors, 27.65% (112/405) had donated for 2~3 times, and 25.68% (104/405) donated more than 4 times. 53.59%(97/181), 23.7%(43/181) and 22.65%(41/181) of the above three groups of blood donors worried about the needles, and 55.48%(81/146), 22.60%(33/146) and 21.92%(32/146) worried about the blood outflow, 52.69% (88/167), 28.14% (47/167), and 19.16% (32/167 )worried about the pain during blood collection (P<0.05). The anxiety of unqualified blood test was similar to that of poor service (P>0.05). There were differences in blood donation experience among the three groups (P<0.05), and gender (P<0.05) was its influencing factor showed by binary Logistic regression analysis. 【Conclusion】 The majority of blood donors, who have donated at the street sites of Nanjing, are worried during blood donation collection. Therefore, the blood centers should provide high-quality services and humanized nursing interventions as well as strengthen the citizens′ awareness of blood donation.

Objective:To investigate the influencing factors for pancreatic endocrine and exocrine insufficiency after pancreaticoduodenectomy.Methods:The retrospective case-control study was conducted. The clinicopathological data of 168 patients who underwent pancreaticoduodenectomy in the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2017 were collected. There were 96 males and 72 females, aged (64±13)years, with a range from 38 to 75 years. Of the 168 patients, 36 had pancreatic endocrine insufficiency while 8 had pancreatic exocrine insufficiency preoperatively. All patients underwent pancreaticoduodenectomy. Observation indications: (1) surgical situations and follow-up; (2) analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy; (3) analysis of influencing factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Follow-up using out-patient examination and telephone interview was performed to detect postoperative condition of blood glucose control, diet and nutrition, tumor recurrence and metastasis up to June 2018. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Surgical situations and follow-up: all the 168 patients underwent pancreaticoduodenectomy successfully and recovered well after operation. All patients were followed up for 6 months. The level of fasting and postprandial blood glucose of the 168 patients after surgery were 7 mmol/L(range, 5-9 mmol/L) and 10 mmol/L(range, 7-14 mmol/L), respectively. The defecation frequency was (2.4±1.2)times per day. No tumor recurrence or metastasis occurred in either patient. One hundred and thirty-two of the 168 patients were included in the study excepting patients with pancreatic endocrine insufficiency before operation. At postoperative 6 months, 47 patients developed pancreatic endocrine insufficiency, with an incidence of 35.61%(47/132). One hundred and sixty of the 168 patients were included in the study excepting patients with pancreatic exocrine insufficiency before operation. At postoperative 6 months, 68 patients had pancreatic exocrine insufficiency, with an incidence rate of 42.50%(68/160). (2) Analysis of influencing factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that gender, metabolic syndrome, chronic pancreatitis, excision point, and postoperative chemotherapy were the related factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy ( χ2=5.300, 6.270, 4.473, 4.392, 5.397, P<0.05). Results of multivariate analysis revealed that male and metabolic syndrome were independent risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy [ hazard ratio ( HR)=5.252, 5.364, 95% confidence interval ( CI): 1.362-6.382, 1.891-12.592, P<0.05)]. (3) Analysis of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy. Results of univariate analysis showed that body mass index (BMI), chronic pancreatitis, total bilirubin, excision point, postoperative pancreatic fistula as grade B or C, and pancreatic fibrosis were related factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( χ2=1.691, 4.910, 7.763, 5.605, 4.663, 7.700, P<0.05). Results of multivariate analysis showed that BMI<18.5 kg/m 2, chronic pancreatitis, total bilirubin ≥171 μmol/L were independent risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy ( HR=3.695, 5.231, 7.623, 95% CI: 1.232-7.324, 2.161-6.893, 1.562-5.235, P<0.05). Conclusions:Male and metabolic syndrome are risk factors for pancreatic endocrine insufficiency after pancreaticoduodenectomy. BMI<18.5 kg/m 2, chronic pancreatitis, and total bilirubin ≥171 μmol/L are risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy.

Objective To study the effect and safety of ticagrelor on platelet in ＞75 years old patients undergoing PCI.Methods One hundred and twenty ＞75 years old patients with acute coronary syndrome undergoing PCI were randomly divided into observation group treated with aspirin+ticagrelor (n =60) and control group treated with aspirin+ clopidogrel (n =60).They were followed up for 1 year after PCI.The major adverse cardiovascular events (MACE),bleeding events,drug-related side effects and all-cause mortality were compared between the two groups.Results No instent thrombosis occurred in any patients,myocardial infarction occurred in 2 patients,angina pectoris occurred in 5 patients and 3 patients died in observation group after 1 year of PCI.Instent thrombosis occurred in 4 patients,myocardial infarction occurred in 3 patients,angina pectoris occurred in 6 patients,and 4 patients died in control group after 1 year of PCI.The incidence of instent thrombosis was significantly lower while that of mild dyspnea was significantly higher in observation group than in control group (0％ vs 6.7％,10.0％ vs 0％,P＜0.05).Conclusion Ticagrelor can effectively prevent instent thrombosis and does not increase the risk of bleeding in ＞75 years old patients after PCI.