Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Background and Aims:Portal hypertensive colopathy(PHC)is a common complication of portal hypertension in patients with liver cirrhosis.It may lead to gastrointestinal bleeding,yet its underlying pathogenesis remains unclear,and systematic research in China is limited.This study aimed to analyze the colonoscopic features in cirrhotic patients and to explore their associations with relevant clinical factors.Methods:A retrospective analysis was conducted on 99 cirrhotic patients who underwent colonoscopy at Xingtai People's Hospital between July 2020 and December 2024.Colonoscopy,gastroscopy,and clinical data were reviewed.Differences between patients with PHC and those without were compared in terms of sex,Child-Pugh classification,platelet count,presence of ascites,and hepatic encephalopathy.Multivariate logistic regression was used to identify independent risk factors for PHC.Additionally,colorectal lesion detection rates were compared with those of a contemporaneous cohort of 444 participants undergoing national colorectal cancer(CRC)screening at the same center.Results:Among the 105 patients with cirrhosis,the detection rates of PHC,adenomatous polyps,and CRC were 32.32%,28.28%,and 3.03%,respectively,while only 37.37%had no abnormal findings.No serious colonoscopy-related complications were observed.The proportion of males in the PHC group was significantly higher than in the non-PHC group(78.13%vs.50.75%,P=0.009).The PHC group also showed significantly higher rates of Child-Pugh class B/C,and lower platelet count(all P<0.05).There was no statistically significant difference in the incidence of ascites and hepatic encephalopathy between the two groups(P>0.05).Multivariate analysis identified that male gender(OR=3.307,95%CI=1.219-8.971)and Child-Pugh class B/C(OR=2.867,95%CI=1.046-7.861)were independent risk factors for PHC.Compared to the CRC screening cohort,cirrhotic patients had a similar adenoma detection rate(28.28%vs.25.00%,P=0.499),and a slightly higher colorectal cancer detection rate that did not reach statistical significance(3.03%vs.0.68%,P=0.135).Conclusion:Colonoscopy revealed a high rate of abnormalities in cirrhotic patients,with PHC and adenomatous polyps being the most common findings.Routine colonoscopy is recommended for cirrhotic patients without contraindications,especially males,and patients with Child-Pugh class B/C,to facilitate early detection of PHC and precancerous lesions,thereby reducing the risk of lower gastrointestinal bleeding and missed diagnoses of malignancy.

Objective To assess the clinical value of multimodal ultrasound score for assessment of endometrial receptivity among patients with polycystic ovary syndrome (PCOS), and to provide guidance for improving pregnancy outcomes among PCOS patients. Methods A total of 48 PCOS patients admitted to Jiangning Hospital Affiliated to Nanjing Medical University between January and December 2023 were enrolled as the case group, while 50 healthy women of childbearing age received ovulation monitoring at the same hospital during the same period served as the control group. Subjects received two-dimensional grayscale ultrasound during the implantation window (19 to 23 days of the menstrual cycle) for measurement of endometrial thickness, Gonen classification, and endometrial peristalsis. Two-dimensional color Doppler ultrasound was used for assessment of endometrial blood flow and three-dimensional ultrasound was used for assessment of endometrial volume and vascularization flow index (VFI). The endometrium multimodal ultrasound scores were estimated, and various parameters were compared between the two groups. The diagnostic performance of these parameters for PCOS was evaluated with receiver operating characteristic (ROC) curves. Results The age of subjects in the case group ranged from 20 to 38 years, with a mean age of (28.20 ± 2.82) years, and their body mass index (BMI) ranged from 21.23 to 29.11 kg/m², with a mean BMI of (26.25 ± 1.60) kg/m². The age of subjects in the control group ranged from 22 to 38 years, with a mean age of (28.10 ± 1.99) years, and their BMI ranged from 21.33 to 29.03 kg/m², with a mean BMI of (26.10 ± 1.78) kg/m². There were no significant differences between the case and control groups in terms of mean age, BMI, estradiol, and testosterone (t = 0.218, 0.422, 0.010, and 0.221; all P > 0.05). The endometrial thickness, endometrial volume, and VFI were significantly higher in the control group than in the case group (t = 4.838, 4.978, and 7.115; all P < 0.05). There were significant differences between the two groups in terms of endometrial classification, endometrial peristalsis pattern, and endometrial and sub-endometrial blood flow (Z = −4.136, −4.048, and −3.884; all P < 0.05). The scores of endometrial classification, endometrial peristalsis, endometrial and sub-endometrial blood flow, endometrial volume, VFI, and multimodal ultrasound were significantly lower in the case group than in the control group (t = 4.539, 4.449, 4.205, 3.209, 5.206, and 4.495; all P < 0.05). No significant difference was detected in the endometrial thickness score between the two groups (t = -0.149, P = 0.882). The areas under the ROC curves for endometrial thickness, endometrial volume, VFI, and multimodal ultrasound scores in diagnosis of PCOS were 0.753, 0.747, 0.809, and 0.858, respectively. Conclusion Multimodal ultrasound score provides a comprehensive assessment of the endometrium, and is effective in the assessment of endometrial receptivity, which may provide a reference for guiding pregnancy planning in PCOS patients.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Objective:To compare the value of coronary CT angiography, congenital heart disease CT, and transthoracic echocardiography (TTE) in the diagnosis of sinus venosus atrial septal defect (SVASD), to summarize the CT image features of SVASD, and to explore its significance in guiding the selection of surgical procedures.Methods:A total of 443 patients of SVASD diagnosed by surgical procedures from January 2017 to December 2021 were retrospectively analyzed. All patients underwent coronary CT angiography or congenital heart disease CT examination and TTE before surgery. Using surgical results as the gold standard, McNemar test was used to analyze the differences between CT and TTE in distinguishing SVASD and pulmonary venous drainage. The difference of pulmonary venosus drainage was analyzed between superior sinus venosus atrial septal defect (ASD) and inferior sinus venosus ASD. The image features of SVASD were summarized and the corresponding surgical procedures were analyzed.Results:No significant difference was found between CT and TTE for the diagnostic accuracy of the SVASD (63.21%, 57.56%, P=0.065). There were 159 patients (35.89%) with PAPVC and 284 patients (64.11%) without PAPVC in the 443 SVASD patients. The diagnostic accuracy of CT and TTE in diagnosing pulmonary venous drainage was statistically significantly different (98.42%, 73.81%, P<0.001). Among 145 patients with superior sinus venosus ASD, 101 (69.66%) were associated with PAPVC; in contrast, among 298 patients with inferior sinus venosus ASD, 58 (19.46%) had PAPVC. The difference between the two groups was statistically significant ( χ 2=106.79, P<0.001), indicating a higher prevalence of PAPVC in patients with superior sinus venosus ASD. The CT imaging features of SVASD can be categorized into four types. The first type was SVASD alone without PAPVC, comprising 284 patients (64.11%). Surgical intervention for this type typically involved direct suturing or closure using a patch. The second type was SVASD with concomitant PAPVC, encompassing 151 patients (34.09%). This type included superior sinus venosus ASD with anomalous pulmonary venous low connection and inferior sinus venosus ASD with PAPVC. During the repair of the defect, it was necessary to redirect the anomalous pulmonary veins into the left atrium. The third type was superior sinus venosus ASD in 7 patients (1.58%). The position of pulmonary vein draining into superior vena cava was too high to be directly corrected to the left atrium, requiring Warden′s technique. The fourth type was rare (1 patient, 0.22%). The anomalous pulmonary vein drained into the coronary sinus. The surgery included incision of the roof of the coronary sinus to redirect pulmonary vein flow to the left atrium, reconstruction of the roof of the sinus to drain coronary vein back to the right atrium, and repair of the ASD. Conclusions:Both CT and TTE can diagnose the type of SVASD, and CT is more accurate than TTE in the diagnosis of PAPVC. CT image features of SVASD can provide valuable information for surgical procedures and guide the selection of surgical procedures.

Objective:To compare the clinical efficacy of rotator cuff repair combined with transposition of the long head of the biceps tendon in the treatment of massive rotator cuff tears with or without subscapularis injury.Methods:A total of 73 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair combined with transposition of the long head of the biceps tendon in the Department of Upper Arm, Sichuan Orthopaedic Hospital from January 2019 to September 2022 were retrospectively analyzed, including 35 males and 38 females, aged 58.8±7.6 years (range, 46-73 years). There were 11 cases on the left side and 62 cases on the right side. Causes of injuries: 6 cases of car accidents, 13 cases of fall injuries, 54 cases of no obvious cause of injury. The patients were divided into subscapularis injury group (37 cases) and no subscapularis injury group (36 cases) according to the subscapularis injury or not. The visual analogue scale (VAS), Constant - Murley score, University of California Los Angeles (UCLA) shoulder score and range of motion were used to evaluate shoulder pain and functional improvement. MRI of the shoulder was taken at the final follow-up and the rotator cuff was assessed for retear using Sugaya grading.Results:All patients successfully completed the operation. The VAS score at 1 year postoperatively in the group without subscapularis injury was 0.58±0.87, which was less than 1.16±1.14 in the group with subscapularis injury ( t=-2.426, P=0.018). The Constant-Murley score and UCLA score at 1 year postoperatively in the group without subscapularis injury were 94.03±6.19 and 32.94±2.59, respectively, which were greater than those of the group with subscapularis injury, which were 86.51±11.96 and 30.38±3.33, and the difference was statistically significant ( P<0.05). Anterior flexion and body external rotation at 1 year postoperatively in the group without subscapularis injury were 137.22°±26.79° and 54.72°±13.20°, which were greater than those in the group with subscapularis injury of 121.08°±22.83° and 38.65°±17.19°, and the difference was statistically significant ( P<0.05), and the difference between the two groups in body internal rotation was not statistically significant ( P>0.05). The subacromial spacing at 1 year postoperatively was 9.4±1.3 mm in the group without subscapularis injury and 9.0±1.5 mm in the group with subscapularis injury, and the difference was not statistically significant ( t=1.318, P=0.192). There were 2 cases of rotator cuff retear 1 year after surgery without subscapular muscle injury and 5 cases of subscapular muscle injury. Conclusion:The clinical efficacy of arthroscopic rotator cuff repair combined with transposition of the tendon of the long head of the biceps tendon in the treatment of massive rotator cuff tears with or without subscapularis muscle injury is satisfactory, and the improvement of pain and function is more obvious in patients without subscapularis muscle injury.

Objective To analyze the characteristics and epidemic trends of Mycoplasma pneumoniae(MP)infection among the pa-tients in our hospital,and explore the diagnostic values of interleukin-6(IL-6)and procalcitonin(PCT)detection for MP infection.Methods A retrospective analysis was conducted on the test results of MP nucleic acid and clinical data,including age,gender,sam-pling date,and treatment category of the 1 122 pneumonia patients in our hospital from September 1,2022,to August 31,2023.The positive detection rate of MP nucleic acid was analyzed in different genders,ages,visit categories,and seasons.Receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic value of IL-6 and PCT levels,and their ratio values in Mycoplasma pneumoniae pneumonia(MPP).Results Among the 1 122 pneumonia patients,the overall positive detection rate of MP was 24.96％.The positive detection rates of MP nucleic acid in male and female patients were 23.28％and 27.29％,respectively,with no statistical-ly significant difference(P＞0.05).The median age of MP nucleic acid-negative patients was 37 years,while that of MP nucleic acid-positive patients was 7 years,showing a statistically significant difference(P＜0.01).MP nucleic acid-positive patients were mainly concentrated in the age groups of 1 to 2 years(20.37％),3 to 5 years(25.60％),and 6 to 8 years(67.40％).The positive detection rates of MP nucleic acid among 913 inpatients and 209 outpatients were 22.45％and 35.89％,respectively,with statistically significant difference(P＜0.01).The highest MP nucleic acid positive detection rate was observed in autumn(42.47％).MP could be co-infected with five other respiratory pathogens in which human rhinovirus(HRV)was the most common(17 cases).ROC curve analysis showed that the IL-6/PCT ratio had the best diagnostic performance for MP infection in the patients with all ages,with an area under the curve(AUCROC)of 0.746,superior to IL-6 and PCT alone.For MP-susceptible patients aged 6 to 8 years,IL-6 had the highest predictive value for MP infection,with an AUCROC of 0.767.Conclusions MPP tends to be epidemic in autumn,with children aged 6 to 8 years being the main susceptible population.The IL-6/PCT ratio is expected to become an auxiliary diagnostic and prognostic evaluation indi-cator for MPP.IL-6 levels have the highest predictive value for MP infection in the susceptible population.