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*

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*

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

Objective To explore the antimicrobial resistance of carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from blood and the related risk factors for infection in patients.Methods Clinical data of 383 KP-infected patients from whose blood Klebsiella pneumoniae(KP)were isolated during hospitalization period in a hos-pital from January 2018 to December 2021 were retrospectively analyzed.Patients were divided into CRKP group(n=114)and non-CRKP group(n=269)based on antimicrobial resistance.According to the prognosis,114 patients in the CRKP group were subdivided into the death group(n=30)and the survival group(n=84).General informa-tion,underlying diseases,antimicrobial use,and infection outcomes of two groups of patients were compared,and risk factors for infection and death after infection were analyzed.Results The resistance rates of KP to tigecycline and compound sulfamethoxazole showed upward trends,with statistically significant differences(both P=0.008).The CRKP group had higher resistance rates to amikacin,aztreonam,compound sulfamethoxazole,ciprofloxacin,cefepime,cefoperazone/sulbactam,piperacillin/tazobactam,tigecycline,ceftazidime,tobramycin,and levofloxacin,as well as higher in-hospital mortality than the non-CRKP group,with statistically significant differences(all P＜0.05).Acute pancreatitis prior to infection(OR=16.564,P＜0.001),hypoalbuminemia(OR=8.588,P＜0.001),stay in in-tensive care unit prior to infection(OR=2.733,P=0.017),blood transfusion(OR=3.968,P=0.001),broncho-scopy(OR=5.194,P=0.014),surgery within 30 days prior to infection(OR=2.603,P=0.010),and treatment with carbapenems(OR=2.663,P=0.011)were independent risk factors for the development of CRKP blood-stream infection(BSI).Cardiac insufficiency before infection(OR=11.094,P=0.001),combined with pulmonary infection(OR=20.801,P=0.010),septic shock(OR=9.783,P=0.002),disturbance of consciousness(OR=11.648,P=0.001),and receiving glucocorticoid treatment(OR=5.333,P=0.018)were independent risk factors for mortality in patients with CRKP BSI.Conclusion The resistance rate of KP from BSI to tigecycline and com-pound sulfamethoxazole presents upward trend.Underlying diseases,invasive procedures,and carbapenem treat-ment are closely related to CRKP BSI.Cardiac insufficiency,pulmonary infection,septic shock,disturbance of con-sciousness,and glucocorticoid treatment can lead to death of patients with CRKP BSI.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

Objective To evaluate the immunogenicity of inactivated quadrivalent influenza vaccine (QIV) in people over 60 years old. Methods Databases including PubMed, EMBASE, Cochrane Library, China Biology Medicine disc, Wangfang Database and China National for Biotechnology Information were searched for random control studies comparing and analyzing the immunogenicity and safety between QIV and inactivated trivalent influenza vaccine (TIV) in people over 60 years old. Meta-analysis of the included literature data was performed using Stata11.0 software. Results A total of 9 articles were included in this study. There was no difference in seroconversion rates (SCR) and seroprotection rates (SPR) for the same vaccine strain after inoculation between QIV and TIV, while for the B vaccine strain (B/Victoria or B/Yamagata) not included in TIV, the SCR and SPR of QIV were significantly higher: SCR RR of 2.04 (95%CI:1.48~2.83) and SPR RR of 1.21 (95%CI:1.11~1.31) for B/Victoria; SCR RR of 2.35 (95%CI:2.04~2.69) and SPR RR of 1.12 (95%CI:1.02~1.23) for B/Yamagata. Conclusion For people over 60 years old, QIV has good immunogenicity, and produces better immunogenicity against influenza B vaccine strains not included in TIV.

Objective To study the effect of berberine on the damage of renal tubular epithelial cells(RETC)in diabetic in vitro.Methods RTEC were divided into control group,model group(high glucose),low dose experimental group(2 mg·L-1 berberine and high glucose),medium dose experimental group(4 mg·L-1 berberine and high glucose),high dose experimental group(8 mg·L-1 berberine and high glucose),BBM-H+miR-NC(transfected with mimics control group,8 mg·L-1 berberine and high glucose),BBM-H+miR-135b group(transfected with miR-135b mimics,8 mg·L-1 berberine and high glucose).Methyl thiazolyl tetrazolium(MTT)method was used to detect cell proliferation activity,flow cytometry was used to detect cell apoptosis rate,Western blot was used to detect the expression of B-cell lymphoma-2(Bcl-2)and Bel-associated X(Bax)proteins in cells,and reactive oxygen species(ROS)level were detected by chemical fluorescence method,thiobarbituric acid method was used to detect malondialdehyde(MDA)level,and xanthine oxidation method was used to detect superoxide dismutase(SOD)level,the levels of tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1 β)were detected by enzyme-linked immunosorbent assay(ELISA).Results The proliferative activity(OD value)of RTEC in control group,model group and low,medium,high dose experimental groups were 0.66±0.04,0.36±0.02,0.43±0.03,0.54±0.03,0.63±0.05;the apoptosis rates were(3.62±0.31)％,(29.41±2.33)％,(20.10±1.65)％,(15.02±1.25)％,(9.58±1.43)％;MDA were(1.04±0.12),(5.24±0.29),(3.45±0.22),(2.16±0.13),(1.60±0.11)nmol·mL-1;SOD were(240.22±12.06),(130.56±10.84),(169.62±12.50),(201.97±12.78),(236.74±14.52)U·mL-1;TNF-α were(31.25±2.51),(51.84±4.20),(44.52±2.61),(38.25±1.50),(32.10±1.78)mg·L-1;IL-8 were(10.59±1.14),(19.95±1.74),(16.10±1.03),(13.52±1.25),(11.17±0.92)mg·L-1;IL-1β were(23.01±1.45),(56.92±2.51),(43.20±1.96),(32.05±1.23),(26.37±2.48)mg·L-1.There were statistically significant differences between model group and control group(all P＜0.05).Compared with the model group,the above indexes in low,medium and high dose experimental group were statistically significant(all P＜0.05).The above indexes of BBM-H+miR-NC group were statistically significant compared with those of BBM-H+miR-135b group(all P＜0.05).Conclusion Berberine can reduce diabetic renal tubular epithelial cell damage by down-regulating miR-135b.

Objective To evaluate the efficacy of two kinds of biliary stent placement in the treatment of high bile duct carcinoma.Methods the clinical data of 136 patients with hilar cholangiocarcinoma who underwent biliary stent implantation in Nanyang Central Hospital from January 2021 to September 2023 were analyzed retrospectively.According to the mode of biliary stent placement,the patients were divided into ERCP group(n=86)and transoral cholangiopancreatoscopy group(n=50).In this study,SPSS26.0 was used for analysis.The age,related test indexes,days of hospitalization,postoperative complications,incidence of liver failure,remission rate of jaundice,stent material and patency rate were observed in the two groups.Results all patients completed the operation successfully.The two groups compared the incidence of postoperative liver failure,postoperative remission rate of jaundice,different material stents,postoperative complications and short-term patency rate,there was no significant statistical significance(P＞0.05).There were significant differences in postoperative complications between the two groups(t=12.02,P＜0.05).Compared with postoperative biliary tract infection and postoperative bleeding,the postoperative biliary tract infection and postoperative bleeding in ERCP group were 26.7％and 11.6％respectively,which were significantly higher than those in transoral cholangiopancreatoscopy group 10.0％and 2.0％(x2=5.42,3.94;P＜0.05).Conclusion of the mean hospitalization days between the two patient groups,Transoral cholangioscopy(10.78±2.17)d＜ERCP(12.91±2.96)d.Compared with the 7th day after operation,the liver function of the two groups was significantly improved and the related test indexes decreased significantly.There was no significant difference in postoperative complications and short-term patency rate between plastic stent and metal stent(P＞0.05).When the patency time was more than 6 months,the patency rate of metal stent was significantly higher than that of plastic stent(P＜0.05).Conclusion The placement of bile duct stent by ERCP and Oral choledochoscopy is effective in relieving clinical symptoms of high cholangiocarcinoma and can improve the quality of life of patients.Transoral cholangiopancreatoscopy has low complication rate,faster recovery,greater advantage,but higher cost;plastic stents are beneficial for patients with short expected survival time,and metal stents are more suitable for patients with long expected survival time.

Objective To understand the research hotspots and development trend of Hedyotidis Herba;To provide reference for related clinical studies.Methods The literature on Hedyotidis Herba was retrieved from CNKI,Wanfang Data,VIP and CBM from January 1,2003 to September 5,2023.NoteExpress 3.7 software was used to manage the bibliothems,and CiteSpace 6.2.R2 software was used to visualize the authors,institutions and keywords.Results Totally 2 713 articles were included,and the annual number of publications showed a fluctuating upward trend.There were 617 source journals,among which Shaanxi Journal of Traditional Chinese Medicine published the most articles(136).799 authors were involved,and the core authors included Liu Jian,Lin Jiumao,Peng Jun,etc.The main research institutions were Nanjing University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine and so on.In recent years,high-frequency keywords were experience of famous doctors,data mining,medication law,apoptosis,lung cancer,liver cancer,etc.The research frontier involved the mechanism,data mining and molecular docking.Conclusion The study of the Hedyotidis Herba mainly focuses on disease treatment,compatibility application,component analysis,mechanism,and the experience summary of clinical application of the Hedyotidis Herba.Data mining for medication law of famous doctors,prediction of potential drug targets through network pharmacology and molecular docking technology and exploration of their mechanisms are the research trends in this field.