OBJECTIVE Aimed at investigating whether reflux pharyngitis is an independent risk factor for the failure of type Ⅰ tympanoplasty for chronic otitis media.This is achieved by analyzing the relationship between the postoperative tympanic membrane healing in patients who underwent type Ⅰ tympanoplasty and pharyngolaryngeal reflux finding score(RFS).METHODS Patients who underwent type Ⅰ tympanoplasty in the Department of Otolaryngology Head and Neck Surgery,Nanshan People's Hospital,Shenzhen,China,from January 2023 to July 2024 were retrospectively included.All the patients received preoperative perfect nasal endoscopy,laryngoscopy,evaluation by the RFS questionnaire,preoperative otoscopy for tympanoplasty,pure tone hearing threshold,and temporal bone thin-layer CT examination.Postoperative otoscopic examination was performed to observe tympanic membrane healing and followed up for 3 months.The patients were divided into surgery success group and failure group based on the criterion of whether a complete tympanic membrane was formed by endoscopic examination within 3 months.The RFS scores of the two groups were statistically analyzed.RESULTS A total of 135 patients with an average age of 44.78 years(±12.22 years)took part in this study,with 60 males and 75 females included,and 68 left ears and 67 right ears involved.There were 120 patients in the surgery success group,and 15 patients in the failure group.Statistical analysis revealed that the RFS score of the patients in the tympanoplasty failure group was remarkably higher than that of the patients in the tympanoplasty success group.Moreover,there were significantly more cases with suspected reflux pharyngitis in the surgery failure group(P=0.007).Reflux-induced tympanic membrane lesion and reperforation mostly occurred in the central part of the tympanic membrane graft.CONCLUSION Reflux pharyngitis has been implicated with tympanoplasty failure,and thus may be a causative factor.Additionally,the RFS can be used to screen patients with chronic suppurative otitis media for suspected reflux pharyngitis.Findings from this work indicate that perioperative anti-reflux therapy,combined with dietary and lifestyle counselling for the patients who suffer from reflux pharyngitis and are about to undergo the tympanoplasty surgery may improve surgical success rate.

Objective To investigate the correlation of peripheral blood follicle suppressor-like protein L(FSTL-1)and chitosanidase 1(CHIT-1)levels with cardiovascular diseases(CVD)in hemodialysis patients and their clinical value.Methods A total of 150 hemodialysis patients treated in Chongqing Liangjiang New Area People's Hospital from January 2021 to June 2023(case group)and 60 healthy people who underwent medical checkups(control group)were selected.The case group consisted of 62 patients who had CVD(CVD group)and 88 patients who did not have CVD(non-CVD group).Enzyme-linked immunosorbent assay was used to detect the levels of FSTL-1 and CHIT-1 in peripheral blood.The levels of FSTL-1 and CHIT-1 among the groups were compared,and the correlation between the levels of FSTL-1 and CHIT-1 with the Gensini scores,high-sensitivity C-reactive protein(hs-CRP),troponin T(cTnT),and left ventricular ejection fraction(LVEF)were analyzed by Pearson's correlation test.Multivariate Logistic regression was used to analyze the influencing factors affecting the occurrence of CVD.Receiver operating characteristic(ROC)curve was used to assess the predictive efficacy of FSTL-1 and CHIT-1 for the occurrence of CVD.Results The levels of FSTL-1 and CHIT-1 were higher in the CVD group and non-CVD group than those in the control group(F=229.200,273.200,P＜0.05),and the levels of FSTL-1 and CHIT-1 in the CVD group were higher than those in the non-CVD group(P＜0.05).The peripheral blood FSTL-1 and CHIT-1 levels in hemodialysis patients were positively correlated with Gensini score,cTnT,hs-CRP(r=0.662,0.724,0.712,r=0.679,0.502,0.341,P＜0.05)and negatively correlated with LVEF(r=-0.463,-0.581,P＜0.05).Compared with the non-CVD group,CVD group had longer chronic kidney disease duration,higher hs-CRP,cTnT,Gensini score,FSTL-1,CHIT-1(P＜0.05),and lower LVEF(P＜0.05).High levels of cTnT,FSTL-1,and CHIT-1 were independent risk factors for CVD in hemodialysis patients(P＜0.05).The area under the curve of the com-bined detection of peripheral blood FSTL-1 and CHIT-1 levels for predicting the occurrence of CVD in hemo-dialysis patients was 0.852(95％CI:0.789-0.915),which was significantly larger than those of the single index of FSTL-1 and CHIT-1(Z=-2.084,-3.112,P=0.038,0.002).Conclusion The increased levels of peripheral blood FSTL-1 and CHIT-1 levels in CVD patients are correlated with cardiovascular injury,cardiac function,and inflammatory indexes in hemodialysis patients,which are independent risk factors affecting the occurrence of CVD in hemodialysis patients,and the combined detection of the two could improve the predic-tive efficacy for the occurrence of CVD in hemodialysis patients.

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m -2 . In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.
Humans ; Male ; Patient Satisfaction ; Adult ; Lipectomy/methods* ; Penis/surgery* ; Retrospective Studies ; Treatment Outcome ; Plastic Surgery Procedures/methods* ; Young Adult ; Penile Diseases/surgery* ; Urologic Surgical Procedures, Male/methods*

Objective To explore the efficacy differences between 3 Tesla magnetic resonance imaging with zero echo time(3T MRI ZTE)and high resolution computed tomography(HRCT)in the detection of pulmonary nodules and the classification diagnosis of the lung imaging reporting and data system(Lung-RADS)in sub-health populations.Methods Clinical and imaging data of 93 patients with pulmonary nodules(126 nodules in total)admitted to some hospital from July to December 2023 were retrospectively analyzed.The 126 nodules were categorized into a benign nodule group(n=51)and a malignant nodule group(n=75)using pathological findings as the gold standard.All the patients underwent examinations by 3T MRI ZTE and HRCT to compare the detection rates of the two measures for pulmonary nodules;the missed and misdiagnosis rates of 3T MRI ZTE,HRCT and Lung-RADS grading were contrasted with the postoperative pathological diagnosis results as the gold standard;comparison analyses of 3T MRI ZTE signs and HRCT signs were performed between the two groups and the patients with different Lung-RADS grades;3T MRI ZTE,HRCT and Lung-RADS grading were compared with the receiver operating characteristic(ROC)curve in terms of diagnosis efficacy for pulmonary nodules,and the consistency analysis was carried out.Results No discernible statistical variation was observed in the detection rates of pulmonary nodules between 3T MRI ZTE and HRCT(P>0.05).Lung-RADS grading had the highest rates of missed diagnosis and misdiagnosis,and 3T MRI ZTE and HRCT had similar detection rates.The malignant nodule group was different from the benign nodule group in the 3T MRI ZTE and HRCT signs in terms of lesion size,spiculation sign,lobulation sign,calcifica-tion,pleural indentation sign,cavity sign,boundary and bronchial cut-off sign,with the differences being statistically signi-ficant(all P<0.05).For the patients of Lung-RADS grade 3,the 3T MRI ZTE and HRCT signs had significant differences in terms of lesion size,spiculation sign,lobulation sign,calcification,pleural indentation sign,cavity sign and bronchial cut-off sign(all P<0.05).For the patients of Lung-RADS grade 4A,the 3T MRI ZTE and HRCT signs had significant differen-ces in terms of lesion size,calcification,boundary and bronchial cut-off sign(all P<0.05).For the patients of Lung-RADS grade 4B,the 3T MRI ZTE and HRCT signs had significant differences in terms of lesion size and calcification(all P<0.05).For the patients of Lung-RADS grade 4X,there were no significant differences found between the 3T MRI ZTE and HRCT signs(all P>0.05).HRCT had the highest sensitivity,specificity,accuracy,AUC value,predictive values and Kappa value for benign and malignant nodules,3T MRI ZTE had the values slightly lower than those of HRCT,and Lung-RADS grading had the lowest values when compared with HRCT and 3T MRI ZTE.Conclusion HRCT and 3T MRI ZTE are complementary for the evaluation of pulmonary nodules,and the differences in imaging signs between them show graded dependence.3T MRI ZTE and HRCT have no significant differences in the detection rate of pulmonary nodules,while HRCT gains advanta-ges in differentiating benign and malignant pulmonary nodules,and references are provided for the screening and clinical early diagnosis of pulmonary nodules.[Chinese Medical Equipment Journal,2025,46(9):52-59]

Objective To explore the effect of project-based learning on the training of sharp injury prevention skills in the pre-job training for nursing interns and its impact on the incidence of sharp injuries during internship.Methods Two classes(class A and B),majoring in nursing at Medical College of Nanchang Institute of Technology in March 2023 were selected as the research subjects by convenience sampling method.Coin flipping method was used to designate class A as the routine group and class B as the intervention group.The routine group received rou-tine pre-job training which mainly focused on retrospective intensive training on nursing operation skills.On this ba-sis,the intervention group integrated project-based learning as compensation education on sharp injury prevention skills.Kirkpatrick's four level training evaluation model was adopted to comprehensively evaluate the educational effectiveness at the four progressive levels of"reaction,learning,behavior,and outcome"at corresponding stages.Results 56 nursing interns were included in the class A routine group and class B intervention group,respectively.The course evaluation score(128.67±4.39 vs 117.28±6.55),needlestick protection knowledge cognition score(109.11±4.38 vs 96.44±6.72),safe injection behavior score(38.45±4.91 vs 32.30±5.62),occupational iden-tity score(58.02±8.55 vs 51.77±15.86),and job competency score(82.59±13.35 vs 75.61±15.09)of nursing interns in the intervention group were all higher than those in the routine group,differences were all statistically sig-nificant(all P＜0.05).The incidence of sharp injuries(19.64％ vs 57.14％)and the average frequency of occu-rrence(1.45 vs 2.13)in nursing interns in the intervention group were both lower than those in the control group.The case intervention rate(87.50％ vs 45.59％)and case reporting rate(93.75％vs 32.35％)after sharp injury were both higher than those in the routine group,and the differences were both statistically significant(both P＜0.05).Conclusion Introducing project-based learning in pre-job training for nursing interns can effectively improve their mastery of protection skills,reduce the incidence of sharp injuries during internships,and have important prac-tical value in cultivating their occupational protection abilities.

Objective:To investigate the risk factors influencing mortality in neonates undergoing continuous renal replacement therapy (CRRT).Methods:This retrospective study included 34 neonates with a corrected age of≤28 days who received CRRT at the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, from January 2019 to December 2023. The neonates were divided into a mortality group ( n=16) and a survival group ( n=18) based on whether they died during CRRT. Pre-CRRT blood biochemical indices, general condition, CRRT treatment modes, parameters, and related complications were analyzed using t-tests, Wilcoxon signed-rank tests, and Chi-square tests. Logistic stepwise regression analysis was used to screen for risk factors associated with CRRT mortality. Results:The mortality rate among the 34 neonates was 48.6% (16/34), with a median CRRT age of 17 days (range: 2-33 days). Eleven neonates (32.3%) were preterm, with the youngest gestational age being 27 weeks and the lowest weight before CRRT initiation being 1 700 g. The mortality group had lower urine output 6-12 hours before CRRT initiation and lower critical illness scores compared to the survival group [0.05 (0.02-1.00) ml/(kg·h) vs. 0.50 (0.20-1.05) ml/(kg·h), (64.50±7.10) scores vs. (77.67±3.65) scores, Z or t values were 10.97 and 3.91, respectively]. However, the vasoactive inotropic score (VIS), proportion of coma, and levels of blood potassium, alanine aminotransferase, aspartate aminotransferase, blood ammonia, blood lactic acid, and activated partial thromboplastin time (APTT) were higher in the mortality group compared to the survival group [ (86.88±15.80) scores vs. (55.56±24.31) scores, 11/16 vs. 1/18, (7.02±1.73) mmol/L vs. (5.88±1.53) mmol/L, 274.55(132.50-664.98) U/L vs. 31.10(19.03-110.70) U/L, 688.20 (449.73-3 618.13) U/L vs. 96.65 (44.15-439.00) U/L, 232.75 (70.33-1 310.85) μmol/L vs.77.70 (49.78-919.05) μmol/L, (11.17±3.36) U/L vs. (7.99±2.67) U/L, and (99.57±39.74) s vs. (60.97±31.25) s, with t, χ2, or Z values of－4.39, 14.81,－2.03,－2.72,－11.81,－3.89,－3.06, and－3.17, respectively] (all P<0.05). Logistic regression analysis revealed that pre-treatment VIS value ( OR=1.150, 95% CI: 1.035-1.278), and blood ammonia level ( OR=1.004, 95% CI: 1.002-1.009) were independent risk factors for mortality (both P<0.05). Conclusions:Neonatal CRRT mortality is associated with pre-treatment VIS scores and blood ammonia levels. Attention should be paid to a rapid decreases in urine output, the intensity of vasopressor support, and elevated levels of blood ammonia, blood lactic acid, transaminases, and APTT at the initiation of treatment.

Alzheimer's disease(AD),a progressive dementia,is one of the most common neurodegenerative dis-eases.Clinical trial results of amyloid-β(Aβ)and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing.There are currently no effective strategies for slowing the progression of AD.Herein,we spotlight the dysregulation of lipid metabolism,particularly the elevation of ceramides(Cers),as a critical yet underexplored facet of AD pathogenesis.Our study delineates the role of Cers in promoting microglial pyroptosis,a form of programmed cell death distinct from apoptosis and necroptosis,characterized by cellular swelling,and membrane rupture mediated by the NLRP3 inflammasome pathway.Utilizing both in vivo experiments with amyloid precursor protein(APP)/presenilin 1(PS1)transgenic mice and in vitro assays with BV-2 microglial cells,we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin(ICA),a flavonoid with known antioxidant and anti-inflammatory properties.Our findings reveal a significant increase in Cers levels and pyroptosis markers(NOD-like receptor family,pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain,caspase-1,gasdermin D(GSDMD),and interleukin-18(IL-18))in the brains of AD model mice,indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis.Conversely,ICA treatment effec-tively reduces these pyroptotic markers and Cer levels,thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD.This study not only advances our un-derstanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy,capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2(COX-2)-NLRP3 inflammasome-gasdermin D(GSDMD)axis.Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of tar-geting microglial pyroptosis in AD.