Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To develop a deep learning-based system for real-time recognition and classification of portal hypertensive gastropathy (PHG) and evaluate its ability to assist junior endoscopists.Methods:A total of 2 848 gastroscopy images from 832 patients with liver cirrhosis were selected from Digestive Endoscopy Center databases of Renmin Hospital of Wuhan University, Wuhan Hospital of Traditional Chinese and Western Medicine, and the Second Hospital of Jingzhou from January 2015 to October 2023. This system referred to 3 endoscopic features of Baveno Ⅱ scoring system. Three models were developed respectively for gastric antral vascular ectasia (GAVE), mosaic-like pattern (MLP), and red marks (RM). The specific classification references were as follows: (1) GAVE model: 0 no, 1 yes; (2) MLP model: 0 no, 1 mild, 2 severe; (3) RM model: 0 no, 1 isolated, 2 fused. The classification results for endoscopic characteristics of PHG of 3 endoscopy experts were taken as the gold standard. The yolov8-m model was used for training. The training dataset, validation dataset, and test dataset were allocated at a ratio of 8∶1∶1. The test dataset was used to evaluate the performance of models and their auxiliary effects on endoscopists. The accuracy, recall, precision, specificity and Kappa coefficient were calculated. Results:The accuracy, recall, specificity of GAVE model were 96.0% (48/50), 87.5% (7/8) and 97.6% (41/42). There was no significant difference between its accuracy and the gold standard ( χ2=316.226, P=1.000). The precision of GAVE1 and GAVE0 were 87.5% (7/8) and 97.6% (41/42) respectively. The accuracy of MLP model was 84.1% (132/157), and there was no significant difference compared with the gold standard ( χ2=3.286, P=0.193). The precision and recall of MLP2 were 88.2% (15/17) and 75.0% (15/20). The precision and recall of MLP1 were 77.9% (60/77) and 88.2% (60/68). The precision and recall of MLP0 were 90.5% (57/63) and 82.6% (57/69). The accuracy of RM model was 87.9% (123/140), and there was no significant difference compared with the gold standard ( χ2=2.891, P=0.409). The precision and recall of RM2 were 94.7% (18/19) and 78.3% (18/23). The precision and recall of RM1 were 72.2% (26/36) and 81.3% (26/32). The precision and recall of RM0 were 92.9% (79/85) and 92.9% (79/85). The mean accuracy of the three junior endoscopists, with and without the assistance of the GAVE model, MLP model, and RM model, respectively increased from 95.3% to 99.3%, from 83.9% to 91.9%, and from 81.9% to 83.1%. The overall consistency analysis of the 3 junior endoscopists with the gold standard indicated that the consistency of the GAVE model before and after assistance was extremely strong (both an overall Kappa of 1.000); the consistency before assistance of the MLP model was moderate (with an overall Kappa of 0.601), which increased to extremely strong after assistance (with an overall Kappa of 0.964); and the consistency of the RM model before and after assistance was also relatively strong (with an overall Kappa of 0.792 before and 0.798 after). Conclusion:The deep learning system accurately identifies and classifies PHG features and significantly enhances diagnostic performance of junior endoscopists.

Objective:To evaluate the effect of baicalein on acute myocardial injury in rats with high-level spinal cord injury (SCI) and the role of nuclear factor E2-related factor 2 (Nrf2).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SCI group, SCI+ baicalein group (SCI+ Bai group) and SCI+ baicalein+ ML385 group (SCI+ Bai+ ML385 group). The high-level SCI rat model was established by the modified Allens method. In Sham group, the 7th cervical vertebra (C 7) was only exposed, but the spinal cord was not hit. In SCI group, C 7 was exposed and the spinal cord was hit. In SCI+ Bai group, baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. In SCI+ Bai+ ML385 group, Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before SCI, and baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. The rats were anesthetized at 24 h after SCI and sacrificed after the blood samples from the abdominal aorta were collected and the hearts were taken for microscopic examination of the pathological changes (by HE staining) which were scored and the ultrastructure of cells (with a transmission electron microscope) and for determination of the serum cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay), content of ferrous ion (Fe 2+ ) in myocardial tissues (by colorimetry), contents of malondialdehyde(MDA) and glutathione (GSH) and activity of superoxide dismutase(SOD) in myocardial tissues (by biochemical method) and expression of glutathione peroxidase 4 (GPX4), acyl CoA synthase long chain family member 4 (ACSl4) and Nrf2 protein and mRNA in myocardial tissues (by Western blot and fluorescent quantitative polymerase chain reaction). The mitochondrial Flameng score was assessed and recorded. Results:Compared with Sham group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 was down-regulated, and the expression of ACSL4 and Nrf2 was up-regulated in SCI group ( P<0.05). Compared with SCI group, the pathological score, mitochondrial Flameng score and serum cTnI concentration were significantly decreased, the contents of Fe 2+ and MDA in myocardial tissues were decreased, the contents of GSH and SOD activity were increased, the expression of GPX4 and Nrf2 was up-regulated, and the expression of ACSL4 was down-regulated in SCI+ Bai group ( P<0.05). Compared with SCI+ Bai group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 and Nrf2 was down-regulated, and the expression of ACSL4 was up-regulated in SCI+ Bai+ ML385 group ( P<0.05). Conclusions:Baicalein can alleviate acute myocardial injury in rats with high-level SCI, and Nrf2 is involved in this process.

Objective:Committee of Minimally Invasive Cardiovascular Surgery(CMICS) conducts an annual summary of minimally invasive cardiovascular surgery procedures performed throughout the country, which includes a comprehensive survey of the total number of minimally invasive procedures by region and the distribution of minimally invasive procedures by hospital. Since CMICS first published the 2018-2019 China Minimally Invasive Cardiovascular Surgery Data White Paper in 2020, the report has received great attention from peers within and outside the industry. In this statistical report, CMICS will focus on publishing the data related to minimally invasive cardiovascular surgery in China from 2021 to 2023 for reference and use by industry peers.

Objective:A retrospective study was conducted to investigate the safety of Percutaneous Endoscopic Gastrostomy(PEG)in elderly patients with Amyotrophic Lateral Sclerosis(ALS)and to identify the factors influencing major complications.The aim is to establish a more robust foundation for optimizing both the procedure and its timing, thereby enhancing the evidence base for refining the surgical approach.Methods:We retrospectively collected clinical data from elderly ALS patients(≥60 years old)who underwent PEG at Peking University Third Hospital between January 2006 and January 2024.This dataset includes information on general health conditions, the progression of ALS, comorbidities, surgical details, and related complications.Additionally, we analyzed the postoperative complications experienced by the included patients, focusing specifically on the risk factors associated with aspiration pneumonia.Results:A total of 140 patients were included in the study, with a mean age of 68.2±5.9 years.Among these, 69 were male(49.3%)with a mean age of 68.4±6.5 years, and 71 were female(50.7%)with a mean age of 67.7±6.0 years.Successful outcomes were observed in 139 cases(99.3%).One case was not completed due to respiratory arrest caused by intraoperative aspiration.Postoperative complications occurred in 36 cases(25.7%), which included 9 cases of wound infection(6.4%), 1 case of abdominal infection(0.7%), 21 cases of aspiration pneumonia(15.0%), 1 case of local fistula leakage(0.7%), 2 cases of transient fever(1.4%), and 2 cases of death during hospitalization(1.4%).Both univariate and multivariate analyses indicated that an onset duration of ≤1 year( P=0.020)and a half-sitting position( P=0.022)significantly influenced the occurrence of aspiration pneumonia, acting as protective factors( β<0, OR<1). Conclusions:PEG is a safe method for providing enteral nutrition to elderly patients with ALS.While most complications associated with the procedure are mild and can be managed, Aspiration pneumonia remains a common and serious complication.However, early surgical intervention and the use of a semi-seated position during the procedure can help reduce the incidence of aspiration pneumonia.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .