1.Mechanistic study on ITGA6 regulation of abdominal wall endometriosis via the PI3K/AKT signaling pathway
Rong GU ; Hailiang HUANG ; Xinrui WANG ; Hanlu LI ; Kaijiang LIU ; Ying ZHU
Acta Universitatis Medicinalis Anhui 2026;61(1):67-74
ObjectiveTo investigate the differential expression of integrin alpha-6(ITGA6) in abdominal wall endometriosis (AWE) tissues and its molecular mechanisms in regulating AWE. Methods36 AWE lesions were designated as the experimental group, while 36 cases of normal endometrial tissues served as the controls. Differential expression of ITGA6 between the two groups was assessed through immunohistochemical (IHC) staining. Human ITGA6 gene-specific interference sequences were designed, synthesized, and packaged into lentiviral vectors to establish the Ishikawa cell line with ITGA6-knockdown. Similarly, the ITGA6-overexpression cell line was constructed using the coding sequence (CDS) of the gene. Real-time PCR and Western blot were performed to detect changes in epithelial-mesenchymal transition(EMT)-related markers and angiogenesis-related indicators. Cell invasion and migration capabilities were assessed by Cell Scratch and Transwell assays. Furthermore, Western blot was conducted to profile PI3K/AKT pathway dynamics. ResultsEctopic endometrial tissues exhibited a marked increase in the number of ITGA6-positive cells and their expression intensity compared to eutopic endometrium (each P < 0.001). Compared with the NC group, the ITGA6-knockdown group showed significantly reduced expression of N-cadherin, VEGF, and TGF-β1 (all P < 0.01), while E-cadherin expression was markedly increased (P < 0.01). Concomitantly, the invasion and migration capacities of ITGA6-low expression were significantly impaired (P < 0.001 for both), accompanied by a marked reduction in AKT and phosphorylated AKT(p-AKT) levels (P < 0.001). Conversely, overexpressing ITGA6 resulted in opposite effects. ConclusionITGA6 modulates EMT and angiogenesis in Ishikawa cells via the PI3K/AKT signaling pathway, thereby enhancing cell invasion and migration capabilities, which contributes to the pathogenesis of AWE.
2.Pathogenesis Evolution and Staged Differentiation and Treatment Strategy of Atherosclerotic Plaques:from the Perspective of "Constraint-Putrefaction-Ulceration"
Hanzheng WANG ; Zhihui LIU ; Hanlu CHEN ; Yilei KONG ; Aisong ZHU
Journal of Traditional Chinese Medicine 2026;67(11):1162-1166
Atherosclerotic plaques arise within the vessels, yet their morphological evolution parallels that of carbuncles and abscesses. Drawing on the pathomechanism progression of carbuncles and abscesses, this paper proposes a dynamic pathogenesis model of "constraint-putrefaction-ulceration" for atherosclerotic plaques. The formation of atherosclerotic plaque begins with phlegm-turbidity obstruction and qi-blood stagnation (constraint stage); prolonged constraint transforms into heat that scorches the vessels and forms plaques (putrefaction stage); ultimately, toxin invades inward and ruptures the vessels, injuring the heart (ulceration stage). Accordingly, staged differentiation and treatments are proposed. During the constraint stage, the focus is venting constraint and unblocking collaterals, clearing and relieving constraint-heat, for which Yue Jyu Pills (越鞠丸) and Danzhi Xiaoyao Powder (丹栀逍遥散) with modifications can be used. During the putrefaction stage, the method is clearing heat and dispelling abscesses, resolving stasis and dissipating knot, with modified Wuwei Xiaodu Beverage (五味消毒饮) and Xuefu Zhuyu Decoction (血府逐瘀汤). During the ulceration stage, it is suggested to expell toxin and stasis, benefit qi and nourish yin using modified Gualou Xiebai Banxia Decoction (瓜蒌薤白半夏汤) and Sheng Mai Powder (生脉散). This framework offers new perspectives for the differentiation and treatment of atherosclerotic plaques in traditional Chinese medicine.
3.Exploration on the Meaning and Treatment of Ge Pulse
Hanzheng WANG ; Hanlu CHEN ; Baizhou WANG
Journal of Zhejiang Chinese Medical University 2025;49(9):1121-1126
[Objective]To explore the pattern,symptom and treatment of Ge pulse,thus promoting the application of pulse diagnosis in clinical practice.[Methods]Through literature collation and theoretical analysis,this study traced the historical evolution of Ge pulse from the Treatise on Cold Damage and Miscellaneous Diseases,reviewed interpretations by various physicians,analyzed the mechanism and characteristics of Ge pulse based on ZHANG Zhongjing's original texts,and summarized four treatment methods,supplemented with case studies.[Results]Ge pulse is characterized by a wiry and large pulse with a weak feeling upon pressure.It reflects a severe condition of internal deficiency and cold,accompanied with dispersion of vital essence,commonly seen in asthenia-related diseases such as blood loss,spermatorrhea,miscarriage and persistent uterine bleeding.ZHANG Zhongjing's treatment methods include:astringing essence with mineral drugs,relieving exterior without inducing profuse sweating,treating according to pathological manifestations,and continuously tonifying deficiency and nourishing essence.Three clinical cases demonstrated that Ge pulse could present in various conditions such as hematochezia,jaundice and febrile diseases with deficiency,all effectively treated with corresponding formulas.[Conclusion]Ge pulse is a critical pulse pattern indicating severe asthenia.Its diagnostic significance and therapeutic system are clear.Clarifying its pattern and corresponding treatment expands the understanding of traditional pulse diagnosis and enhances clinical management of deficiency-related disorders.
4.Exploration on the Meaning and Treatment of Ge Pulse
Hanzheng WANG ; Hanlu CHEN ; Baizhou WANG
Journal of Zhejiang Chinese Medical University 2025;49(9):1121-1126
[Objective]To explore the pattern,symptom and treatment of Ge pulse,thus promoting the application of pulse diagnosis in clinical practice.[Methods]Through literature collation and theoretical analysis,this study traced the historical evolution of Ge pulse from the Treatise on Cold Damage and Miscellaneous Diseases,reviewed interpretations by various physicians,analyzed the mechanism and characteristics of Ge pulse based on ZHANG Zhongjing's original texts,and summarized four treatment methods,supplemented with case studies.[Results]Ge pulse is characterized by a wiry and large pulse with a weak feeling upon pressure.It reflects a severe condition of internal deficiency and cold,accompanied with dispersion of vital essence,commonly seen in asthenia-related diseases such as blood loss,spermatorrhea,miscarriage and persistent uterine bleeding.ZHANG Zhongjing's treatment methods include:astringing essence with mineral drugs,relieving exterior without inducing profuse sweating,treating according to pathological manifestations,and continuously tonifying deficiency and nourishing essence.Three clinical cases demonstrated that Ge pulse could present in various conditions such as hematochezia,jaundice and febrile diseases with deficiency,all effectively treated with corresponding formulas.[Conclusion]Ge pulse is a critical pulse pattern indicating severe asthenia.Its diagnostic significance and therapeutic system are clear.Clarifying its pattern and corresponding treatment expands the understanding of traditional pulse diagnosis and enhances clinical management of deficiency-related disorders.
5.Uniportal thoracoscopic right middle lobectomy via posterior approach in 52 patients: A prospective cohort study
Xiuji YAN ; Hanlu ZHANG ; Longqi CHEN ; Yimin GU ; Wenping WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1281-1287
Objective To explore the short-term surgical outcomes of the modified surgical procedure for uniportal thoracoscopic right middle lobectomy (RML). Methods In this modified approach, the incision was created at sixth or seventh intercostal space inferior to the subscapular angle. The surgeon stood on the opposite side of the operating table. The surgery was performed by serial division of the anterior oblique fissure, the vein, bronchus, artery, and horizontal fissure following the single-direction strategy. As for patients with malignant lesions, hilar and mediastinal lymph node dissection was performed. Clinical characteristics and early surgical outcomes were collected and analyzed. Results Fifty two patients were included in this study in the Department of Thoracic Surgery, West China Hospital, Sichuan University between January 2021 and June 2023. There were 20 males and 32 females at an average age of 48.0±10.5 years. No conversion or perioperative mortality was occurred. Mean surgical time was 68.1±16.8 min, mean blood loss was 16.5±4.9 mL, median chest tube duration was 2 (2-22) d and median postoperative hospital stay was 3 (3-24) d. There was no intraoperative or postoperative complication but one patient developed postoperative prolonged air leak (>5 d). Mean postoperative visual-analog scale on postoperative day 1, day 2 and day 3 was 1.5±0.8, 1.7±0.4, 0.8±0.7, respectively. Conclusion Trans-posterior-approach uniportal thoracoscopic single-direction RML is a safe, feasible, and effective procedure, which provides an appropriate direction and angle for dissection and stapling, solving the challenge of conventional uniportal RML lobectomy.
6.Effect of muscle mass reduction on the progression of coronary artery calcification in maintenance hemodialysis patients
Hanlu WANG ; Qian ZHANG ; Jiaying ZHANG ; Li NI ; Jing QIAN ; Ping CHENG ; Chuhan LU ; Jing CHEN
Chinese Journal of Nephrology 2023;39(2):85-94
Objective:To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis (MHD) patients, and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods:The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1, 2013 to December 31, 2017 were enrolled. This study included cross-sectional study and prospective cohort study. Multi-slice spiral computed tomography was used to measure coronary artery calcification, and coronary artery calcium score (CACS) was calculated. In the cross-sectional study, 62 MHD patients were enrolled. According to baseline CACS, the patients were divided into low calcification group (CACS < 100) and high calcification group (CACS ≥ 100). The nutritional and bone mineral metabolism indexes were compared between the two groups. Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators. Since 6 patients were lost to follow-up, 56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study. According to the progression of CACS, the patients were divided into slow progression group (ΔCACS/year < 100) and rapid progression group (ΔCACS/year ≥ 100). Logistic regression equation was used to analyze the risk factors of coronary calcification progression. Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results:In the cross-sectional study, the age of 62 patients was (62.34±10.82) years old, and the median dialysis age was 78 (39,139) months. Among the 33 male patients, compared with the low calcification group ( n=7), the high calcification group ( n=26) had older age ( t=-2.281, P=0.030) and higher blood triglyceride ( Z=-1.985, P=0.047), and there was no statistically significant difference in muscle mass between the two groups; among the 29 female patients, the muscle mass/height 2 ( t=-2.600, P=0.015) and serum calcium ( t=-2.641, P=0.014) in the high calcification group ( n=15) were both higher than those in the low calcification group ( n=14), and the hemoglobin level was lower ( t=2.531, P=0.018), and the difference in muscle mass between the two groups was not statistically significant. High sensitivity C-reactive protein ( β=0.425, P=0.022) was independently correlated with CACS in male patients, and muscle mass/extracellular water ( β=-0.580, P=0.001) was independently correlated with CACS in female patients. In the prospective cohort study, the age of 56 patients was (59.82±11.14) years old, and the median dialysis age was 82 (40, 146) months. There was no significant difference in all-cause mortality between slow progression group ( n=22) and rapid progression group ( n=34), but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group ( P=0.017). Compared with the slow progression group, the rapid progression group had higher proportion of males ( χ2=4.791, P=0.029), older age ( Z=-2.131, P=0.038), lower baseline muscle mass/extracellular water ( Z=2.482, P=0.016) and high-density lipoprotein cholesterol ( t=2.133, P=0.042), and faster rate of muscle mass loss (Δmuscle mass·height -2·year -1) ( Z=-2.282, P=0.023). Multivariate logistic regression analysis results showed that muscle mass loss ( OR=0.089, 95% CI 0.010-0.792, P=0.030) and baseline CACS ( OR=1.003, 95% CI 1.000-1.005, P=0.021) were influencing factors for progression of coronary artery calcification in MHD patients. Conclusion:Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.
7.Prediction of lipid nanoparticles for mRNA vaccines by the machine learning algorithm.
Wei WANG ; Shuo FENG ; Zhuyifan YE ; Hanlu GAO ; Jinzhong LIN ; Defang OUYANG
Acta Pharmaceutica Sinica B 2022;12(6):2950-2962
Lipid nanoparticle (LNP) is commonly used to deliver mRNA vaccines. Currently, LNP optimization primarily relies on screening ionizable lipids by traditional experiments which consumes intensive cost and time. Current study attempts to apply computational methods to accelerate the LNP development for mRNA vaccines. Firstly, 325 data samples of mRNA vaccine LNP formulations with IgG titer were collected. The machine learning algorithm, lightGBM, was used to build a prediction model with good performance (R 2 > 0.87). More importantly, the critical substructures of ionizable lipids in LNPs were identified by the algorithm, which well agreed with published results. The animal experimental results showed that LNP using DLin-MC3-DMA (MC3) as ionizable lipid with an N/P ratio at 6:1 induced higher efficiency in mice than LNP with SM-102, which was consistent with the model prediction. Molecular dynamic modeling further investigated the molecular mechanism of LNPs used in the experiment. The result showed that the lipid molecules aggregated to form LNPs, and mRNA molecules twined around the LNPs. In summary, the machine learning predictive model for LNP-based mRNA vaccines was first developed, validated by experiments, and further integrated with molecular modeling. The prediction model can be used for virtual screening of LNP formulations in the future.
8.Progresses in clinical treatment of multiple rib fractures and flail chest
Xu SHEN ; Yunke ZHU ; Hanlu ZHANG ; Zeguo ZHUO ; Gang LI ; Tieniu SONG ; Zhijie XU ; Guha ALAI ; Peng YAO ; Xia ZHONG ; Yucheng WANG ; Yidan LIN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(07):858-862
The incidence of rib fracture in patients with chest trauma is about 70%. Simple rib fractures do not need special treatment. Multiple rib fractures and flail chest are critical cases of blunt trauma, which often cause serious clinical consequences and need to be treated cautiously. Nowadays, there is a controversy about the diagnosis and treatment of multiple rib fractures and flail chest. In the past, most of the patients were treated by non-operative treatment, and only less than 1% of the patients with flail chest underwent surgery. In recent years, studies have confirmed that surgical reduction and internal fixation can shorten the hospital stay, and reduce pain and cost for patients with flail chest, but there is still a lack of relevant clinical consensus and guidelines for diagnosis and treatment, which leads to great differences in clinical diagnosis and treatment plans. This article reviewed the treatment, surgical indications and surgical timing of multiple rib fractures and flail chest.
9.The modified minimally invasive esophagectomy using the concept of "single-direction" thoracoscopic technique
Lingli NIU ; Yimin GU ; Yunke ZHU ; Hanlu ZHANG ; Longqi CHEN ; Wenping WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(08):972-978
Objective To explore the safety and feasibility of the modified and improved thoracoscopic surgery for esophageal cancer using the concept of "single-direction" thoracoscopic technique. Methods The clinical data of 65 patients undergoing this modified minimally invasive esophagectomy based on "single-direction" thoracoscopic system between June 2018 and April 2019 were retrospectively analyzed, including 54 males and 11 females aged 62.5±7.8 years. Results The thoracoscopic operation time was 133.4±28.6 min, and intraoperative blood loss was 61.9±29.2 mL. No intraoperative blood transfusion was needed. One patient was transferred to open thoracotomy (due to severe pleural adhesion atresia). Major complications included anastomotic leak, pneumonia, chylothorax, incisional infection, recurrent laryngeal nerve paralysis and gastric emptying disorders, which were recovered by conservative treatment. No postoperative death occurred. The median number of lymph nodes and lymph node station harvested was 19 and 10, respectively. The median postoperative hospital stay was 10 days. The volume of chest drainage was 1 117.3±543.4 mL. Conclusion The minimally invasive operation mode of esophageal cancer based on "single-direction" thoracoscopic system is safe and feasible, and has good field vision and smooth and simplified procedure.
10.Establishment of an evaluation system for thoracoscopic clinical function and applicability
Zihao WANG ; Fuqiang WANG ; Hanlu ZHANG ; Yu ZHENG ; Yun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(08):893-899
Objective By establishing a set of evaluation system for thoracoscopic clinical function and applicability, to evaluate and compare the advantages and disadvantages of different brands of thoracoscopes, and to provide some suggestions for the innovation and upgrade of thoracoscopes, especially for the domestic thoracoscopes. Methods The project coordination team initially formulated the evaluation index system for the clinical function and applicability of thoracoscope by querying literature and brainstorming. The Delphi expert consultation method was used to distribute questionnaires to the selected experts. Experts provided scores which were based on the importance of each indicator, and clarified the basis of their judgment and the familiarity with the evaluation indicators. After two rounds of screening by Delphi method, a thoracoscopic clinical function and applicability satisfactory questionnaire was formed. The appropriate sample for pre-investigation was selected, and the reliability and validity were tested. The index composition was adjusted based on the results of the test to form a final evaluation scale. Results The project coordination team initially formulated 24 thoracoscope-related evaluation indicators. After two rounds of experts consultation, the item "brightness adjustment" was deleted without any additional entries. The positive coefficients of the experts in the first round and the second round were 100.0% and 80.0%, respectively. The two rounds of authoritative coefficients were 0.86 and 0.90, and the coordination coefficients were 0.272 (P<0.001) and 0.523 (P<0.001), respectively. A total of 140 questionnaires were issued in this pre-investigation. The recovery rate was 100.0% and the effective rate was 90.0%. The Cronbach's α value of the scale was 0.936, and the Spearman-Brown split-half reliability coefficient was 0.972. The factor analysis finally extracted 3 common factors. The total variance of the cumulative interpretation was 70.9%. The three common factors were named "operation related", "image related" and "device related". Conclusion The evaluation index system developed in this study has good reliability and validity, and can be used as a tool to evaluate the clinical function and applicability of thoracoscopes.

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