Background: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). In recent years, research on anal CA has primarily focused on treatment rather than underlying mechanisms. The mechanism of HPV persistence and recurrence in CA require further exploration. It needs multiple researches in mechanisms to focalize treatment targets. Objective: To investigate the relationship between intestinal mucosal immunity and the relapse of anal CA and persistent infection. Methods: Levels of interferon gamma (IFN-γ) and secretory immunoglobulin A (sIgA) were measured using enzyme-linked immunosorbnent assay in anal mucosal cells obtained from patients treated at Tianjin Union Medical Center from September 2022 to December 2024. All the participants signed Informed Consent and the whole plan was approved by Institutional Review Board in Tianjin Union Medical Center (No. B155). Results: The levels of IFN-γ and sIgA significantly decreased after infection, and persistent infection exhibited even lower levels. These two factors increased following treatment, reaching peak concentrations at 4 weeks before decreasing again. Conclusion These findings demonstrate a significant association between persistent anal CA infection and dysregulation of intestinal mucosal immunity.

Objective To develop a novel drainage catheter based on the anatomical structure of the mammary duct and establish a non-invasive treatment protocol for patients with acute high-tension breast milk cyst during lactation.Methods Ten primiparous patients with acute high-tension breast milk cyst during lactation,admitted to the postpartum clinics of three hospitals,were enrolled as study subjects.A novel drainage catheter was prepared using an epidural anesthesia catheter,and intubation was performed to unblock the obstructed mammary ducts.For cases with intubation failure,puncture as-piration was employed.Local cold compresses were applied to the breasts after treatment.Results Out of 10 patients,6 were successfully unblocked(successful group),and 4 failed(failure group).The duration of illness in the successful group was(6.00±0.82)days,which was shorter than that in the failure group[(9.50±1.80)days](P＜0.05).The insertion depth of the catheter in the successful group was(6.42±0.67)cm,which was greater than that in the failure group[(4.00±0.71)cm](P＜0.05).There was no statistically significant difference in cyst diameter between the two groups(P＞0.05).For patients in whom unblocking failed,puncture aspiration was performed,and 3 of them experienced recurrence after the initial puncture.Ultrasound-guided re-puncture aspiration and weaning were performed.One patient with evident inflammatory symptoms was administered systemic antibiotic therapy.After treatment,7 patients resumed lactation,and follow-up results indicated that all 10 patients were cured.Conclusion Acute high-tension breast milk cyst during lactation is rela-tively rare in clinical practice.The novel drainage catheter can achieve non-invasive unblocking of distally obstructed mammary ducts in the lactiferous sinus.The comprehensive treatment protocol can improve the overall cure rate and result in a high rate of resumed lactation post-treatment.

Objectives:QT interval prolongation during treadmill test exercise is one of the clinical feature of patients with long QT syndrome(LQTS).This study aimed to explore the feasibility and efficacy of treadmill exercise testing as an auxiliary diagnosis tool for LQTS in clinical practice.Methods:We enrolled normal healthy individuals,common cardiovascular disease patients,and clinically diagnosed or suspected LQTS patients,who underwent treadmill exercise test from July 2023 to July 2024 at Fuwai Hospital.A special treadmill exercise testing procedure was designed to record the QT interval correction(QTc)intervals of the twelve lead electrocardiogram at 6 time points when performing the exercise tablet,including supine,sitting,standing,peak exercise,and recovery at 1-minute and 4-minute.The differences in QTc intervals among healthy group,cardiovascular diseases group,and suspected LQTS group were compared.Results:A total of 80 cases were consecutively enrolled,including 37 normal healthy controls,25 patients with common cardiovascular disease,and 18 patients with suspected LQTS.The QTc intervals at 6 points did not differ significantly between normal healthy controls and patients with cardiovascular disease,with QTc intervals less than 480 ms at all measurement.For patients with suspected LQTS,67.7%(12/18)of these patients presented a QTc interval≥480 ms at the 4-minute during recovery period.Among them,5 cases were confirmed to have pathogenic gene mutations of LQTS by genetic testing(including 1 case with a lying electrocardiogram QTc interval of 489 ms diagnosed with LQTS 1 type and a QTc interval of 636 ms during the 4-minute recovery period after exercise);5 clinically diagnosed patients(negative or undetectable in genetic testing)with a Schwartz score≥4,and the remaining 2 patients had a Schwartz score of 3.The remaining 5/18 patients,include 2 patients with clinical Schwartz scores≥4 and 3 patients with clinical suspicion(Schwartz scores 2-3)had a 4 min QTc interval of 445-480 ms during exercise recovery.Another patient with clinical suspicion(Schwartz score 3)had a 4 min QTc interval of<445 ms during exercise recovery and a negative genetic test at a later stage.Receiver operating characteristic curve analysis showed a sensitivity of 83.3%and specificity of 98.4%for QTc interval≥482 ms during the 4-minute recovery period of exercise as the LQTS diagnostic cutoff.Conclusions:This study results suggest that this special treadmill exercise testing protocol is effective in identifying LQTS and has strong feasibility and generalizability for clinical practice.

Objectives:QT interval prolongation during treadmill test exercise is one of the clinical feature of patients with long QT syndrome(LQTS).This study aimed to explore the feasibility and efficacy of treadmill exercise testing as an auxiliary diagnosis tool for LQTS in clinical practice.Methods:We enrolled normal healthy individuals,common cardiovascular disease patients,and clinically diagnosed or suspected LQTS patients,who underwent treadmill exercise test from July 2023 to July 2024 at Fuwai Hospital.A special treadmill exercise testing procedure was designed to record the QT interval correction(QTc)intervals of the twelve lead electrocardiogram at 6 time points when performing the exercise tablet,including supine,sitting,standing,peak exercise,and recovery at 1-minute and 4-minute.The differences in QTc intervals among healthy group,cardiovascular diseases group,and suspected LQTS group were compared.Results:A total of 80 cases were consecutively enrolled,including 37 normal healthy controls,25 patients with common cardiovascular disease,and 18 patients with suspected LQTS.The QTc intervals at 6 points did not differ significantly between normal healthy controls and patients with cardiovascular disease,with QTc intervals less than 480 ms at all measurement.For patients with suspected LQTS,67.7%(12/18)of these patients presented a QTc interval≥480 ms at the 4-minute during recovery period.Among them,5 cases were confirmed to have pathogenic gene mutations of LQTS by genetic testing(including 1 case with a lying electrocardiogram QTc interval of 489 ms diagnosed with LQTS 1 type and a QTc interval of 636 ms during the 4-minute recovery period after exercise);5 clinically diagnosed patients(negative or undetectable in genetic testing)with a Schwartz score≥4,and the remaining 2 patients had a Schwartz score of 3.The remaining 5/18 patients,include 2 patients with clinical Schwartz scores≥4 and 3 patients with clinical suspicion(Schwartz scores 2-3)had a 4 min QTc interval of 445-480 ms during exercise recovery.Another patient with clinical suspicion(Schwartz score 3)had a 4 min QTc interval of<445 ms during exercise recovery and a negative genetic test at a later stage.Receiver operating characteristic curve analysis showed a sensitivity of 83.3%and specificity of 98.4%for QTc interval≥482 ms during the 4-minute recovery period of exercise as the LQTS diagnostic cutoff.Conclusions:This study results suggest that this special treadmill exercise testing protocol is effective in identifying LQTS and has strong feasibility and generalizability for clinical practice.

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Objective:To discuss the improvement effect of uric acid(UA)on the postoperative cognitive dysfunction(POCD)in the mice anesthetized with isoflurane for a long duration,and to clarify its possible mechanism.Methods:Twenty-four healthy male C57BL/6 mice were randomly divided into blank control group,anesthesia group,and UA group,and there were eight mice in each group.The mice in UA group were injected intraperitoneally with 200 μL UA solution daily for 2 d before anesthesia.The mice in blank control group and anesthesia group were given the same volume of saline;the mice in anesthesia group and UA group were used to prepare the models of long-duration isoflurane anesthesia,while the mice in blank control group were untreated.Y-maze tests was used to detect the alternation success rate,movement distances,and movement speeds of the mice in various groups;situational fear experiment was used to detect the percentages of freezing time;Western blotting method was used to detect the expression levels of interleukin(IL)-1β,IL-10,and mature brain-derived neurotrophic factor(mBDNF)proteins in hippocampus tissue of the mice in various groups.Results:The Y-maze test results showed that compared with blank control group,the alternation success rate of the mice in anesthesia group was significantly decreased(P<0.01);compared with anesthesia group,the alternation success rate of the mice in UA group was significantly increased(P<0.01).The situational fear experiment results showed that compared with blank control group,the percentage of freezing time of the mice in anesthesia group was significantly decreased(P<0.01);compared with anesthesia group,the percentage of freezing time of the mice in UA group was significantly increased(P<0.05).The cued memory experiment resutls showed that there were no significant differences of the percentage of freezing time of the mice between various groups(P>0.05).The Western blotting results showed that compared with blank control group,the expression level of IL-1β protein in hippocampus tissue of the mice in anesthesia group was increased(P<0.01),while the expression levels of IL-10 and mBDNF proteins were decreased(P<0.01);compared with anesthesia group,the expression level of IL-1β protein in hippocampus tissue of the mice in UA group was decreased(P<0.05),and the expression levels of IL-10 and mBDNF proteins were increased(P<0.05 or P<0.01).Conclusion:UA can improve the POCD in the mice,and its mechnasim may be related with its anti-inflammatory activity inhibiting the central inflammation and upregulating the mBDNF protein expression.

Objective:To analyze the factors influencing the theoretical score of graduation examination of standardized residency training in a class-A tertiary general hospital in Shanghai from 2018 to 2021, and establish prediction models, and to provide a reference for further improving the quality of residency training.Methods:We collected the data of 556 residents who participated in the residency training graduation examination at the hospital from 2018 to 2021. Binary regression and logistic regression analyses were used to determine the association of residents' basic information, their routine assessment results at the bases, and the base performance assessment score (indicating the bases' training quality) with theoretical graduation examination results; and prediction models for the theoretical graduation examination score were established, using binary regression and logistic regression methods to construct model datasets. SPSS 26.0 was used for statistical analysis.Results:From 2018 to 2021, a total of 556 people participated in the residency training graduation examination at the hospital. The first-time pass rate of the first station theoretical examination station was 97.48% (542/556). Trainees graduating from double first-class schools had the highest first-time pass rate of 98.09% (359/366); doctoral students had the highest first-time pass rate of 98.59% (140/142); and residents of the two-year training program had the highest first-time pass rate of 98.34% (297/302). According to the binary regression analysis of categorical variables such as residents' basic information, the base level was associated with whether residents passed the theoretical examination ( P<0.05). According to the logistic regression analysis of residents' routine assessment scores and the base performance assessment score, the annual theoretical assessment score, the first-time theoretical score of the national medical licensing examination, the annual professional performance test score, and the base performance assessment score were key factors affecting the theoretical graduation examination score ( P<0.05). In the regression analysis associated with the theoretical graduation examination score, the annual professional performance test score showed the highest regression coefficient and the highest variance inflation factor, indicating strong multicollinearity. Therefore, the annual professional performance test score was important in predicting the theoretical score of the graduation examination. Conclusions:This study used binary regression and logistic regression models to analyze the possible factors affecting the theoretical graduation examination score and the degree of association, and also established two prediction models of the theoretical graduation examination score to predict trainees at risk. Through implementing the concept of hierarchical progression, adding personalized tutoring, realizing information management for residency training, and providing intelligent early intervention, the pass rate of residency training graduation examination is expected to be further improved, ultimately achieving the purpose of improving the quality of residency training.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.