1.Tubeimoside I promoted Snail ubiquitination degradation and inhibited the malignant progression of PANC-1 pancreatic cancer cells
Lixue FENG ; Chunyun ZHANG ; Zeyan LI ; Huiqi YIN ; Yingning SUN ; Dian-hui LIU ; Baogang YU ; He LIU ; Qingzhu YANG
Chinese Journal of Pathophysiology 2025;41(10):1955-1962
AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.
2.Morphological and Histological Study of Gentiana davidii Franch
Jiangli PENG ; Lanchun PENG ; Peng WANG ; Qiuxian PENH ; Qingzhu ZHEN ; Shunxiang LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):375-383
Objective To establish an identification method for Gentiana davidii Franch.Methods Original plants and herbal properties were identified with pharmacognostical method,and its diagnostic characteristics were described.Different tissue parts and whole plant powder of G.davidii Franch.were studied by conventional optical microscopy,scanning electron microscopy combined with various microscopy methods.Results The morphological,trait and microstructure characteristics of G.davidii Franch.were obvious.The microscopic characteristics of the tissues were metazoan cortex visible in the transverse section of the roots,and the casparian strip was obvious in the transverse section of the stems.The epidermis of the leaves showed a cephalic bulge,and the cell wall of the epidermis cells showed a shallow wavy curve.There were stomata and non-glandular hairs in the lower epidermis of the leaves,and the cell walls of the epidermis cells were deeply wavy.The upper epidermis of the petal has a regular arrangement of cerebral striatum spherical protrusions,and the lower epidermis has a regular arrangement of ridge flat elongated protrusions.The pollen grains were oblong with three germination furrows and different sizes of surface decorative mesh.The seed was pear-shaped,the surface was honeycomb,I and II could be seen.Conclusion The microstructure of the features tissue of G.davidii Franch.can provide a basis for its authenticity identification,quality evaluation and formulation of quality standards,and at the same time offer e a new taxonomic basis for the taxonomy of gentian plants.
3.Tubeimoside I promoted Snail ubiquitination degradation and inhibited the malignant progression of PANC-1 pancreatic cancer cells
Lixue FENG ; Chunyun ZHANG ; Zeyan LI ; Huiqi YIN ; Yingning SUN ; Dian-hui LIU ; Baogang YU ; He LIU ; Qingzhu YANG
Chinese Journal of Pathophysiology 2025;41(10):1955-1962
AIM:This study aims to investigate the molecular mechanism by which tubeimoside I(TBMS1)inhibits Snail expression in pancreatic cancer cells(PANC-1).METHODS:Human pancreatic cancer PANC-1 cells were cultured in vitro.The inhibitory effect of TBMS1 on PANC-1 cells was assessed using the MTT assay,and the data were analyzed based on the IC50 value of TBMS1.The impact of TBMS1 on the clonal formation ability of PANC-1 cells was evaluated through colony formation assays.The Transwell assay was employed to assess the effect of TBMS1 on the migrato-ry capability of PANC-1 cells.Apoptosis and cell cycle alterations in PANC-1 cells were analyzed using acridine orange staining and flow cytometry.The expression of Snail protein in pancreatic cancer and its relationship with survival of the patients were analyzed using the GEPIA database and Kaplan-Meier Plotter data.Immunofluorescence staining was con-ducted to investigate the effect of TBMS1 on Snail expression,while Western blot was used to evaluate the expression of poly(ADP-ribose)polymerase(PARP),E-cadherin and Snail in the cells.The ubiquitination of Snail protein was mea-sured using immunoprecipitation techniques.RESULTS:As the concentration of TBMS1 increased,the survival rate and number of clones formed by PANC-1 cells progressively decreased,leading to apoptosis,cleavage of PARP,and cell cycle arrest in the G1 phase.There was also a reduction in the proportion of cells in the S phase and a decrease in cell migration ability.The expression of Snail protein,a critical factor in cell migration,was inhibited,while E-cadherin protein levels were increased.Treatment with the proteasome inhibitor MG132 was able to reverse the suppression of Snail protein ex-pression caused by TBMS1.Immunoprecipitation results indicated that TBMS1 enhances the ubiquitination and subse-quent degradation of Snail protein.CONCLUSION:TBMS1 effectively inhibits the malignant progression of pancreatic cancer cells by promoting the ubiquitination and degradation of Snail protein in PANC-1 cells.
4.Clinical study on transcutaneous electrical acupoint stimulation combined with skin sympathetic response to evaluate autonomic nerve preservation after laparoscopic radical gastrectomy
Qingzhu DING ; Jin GAO ; Huina WANG ; Zhiyi CHENG ; Chuanjiang HUANG ; Guiyuan LIU ; Xiaojun ZHAO ; Xing CHE ; Xiaolan YOU
Chinese Journal of Gastrointestinal Surgery 2025;28(2):178-184
Objective:This study aimed to explore the utility of transcutaneous electrical acupoint stimulation (TEAS) combined with skin sympathetic response (SSR) in assessing the effectiveness of perigastric autonomic nerve preservation during radical gastrectomy.Methods:A retrospective cohort analysis was conducted involving 221 patients who underwent laparoscopic radical gastrectomy at the Department of Gastric Surgery, Taizhou People's Hospital, affiliated with Nanjing Medical University, between June 2022 and September 2024. The cohort comprised 109 patients who underwent laparoscopic radical total gastrectomy without autonomic nerve preservation (total gastrectomy without nerve preservation group). Additionally, 112 patients underwent laparoscopic radical distal gastrectomy, including 34 patients who received autonomic nerve preservation (nerve preservation group) and 78 patients who did not (without nerve preservation group). TEAS was administered at the Zusanli and Tianshu acupoints one day before and one day after surgery, during which SSR latency and voltage amplitudes in the upper and lower extremities were recorded and compared across groups. Differences in SSR latency and voltage amplitude between the nerve preservation and non-nerve preservation groups of the distal gastrectomy cohort were also analyzed. Further, TEAS was applied at the same acupoints for 15 minutes on the 1st, 2nd, and 3rd postoperative days, and changes in intestinal sounds and intestinal functional recovery time were monitored. Surgical parameters, including operative duration, intraoperative blood loss, and harvested lymph node, were documented. Postoperative inflammatory indicators, including interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), and the incidence of anastomotic leakage, were evaluated. At three months postoperatively, gastroscopy was performed to assess residual gastric food and bile reflux. Additionally, the prognostic nutritional index (PNI) was evaluated across all patient groups.Results:Following total gastrectomy, TEAS of Zusanli combined with arms' SSR revealed a latency of (23 59.71±410.55) ms and a voltage amplitude of (0.43±1.67) mV; for the legs, latency was (2 596.88±369.01) ms and voltage amplitude was (0.25±0.08) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (2 746.47±224.37) ms and a voltage amplitude of (0.31±0.14) mV; for the legs, latency was (2 891.90±193.61) ms and voltage amplitude was (0.19±0.72) mV. Postoperative latency was significantly prolonged, and voltage amplitude was markedly reduced (all P < 0.01). In the distal gastrectomy with nerve preservation group, TEAS of Zusanli combined with arms' SSR showed a latency of (1 668.04±261.91) ms and a voltage amplitude of (0.78±0.26) mV; for the legs, latency was (1 568.86±220.09) ms and voltage amplitude was (0.61±0.24) mV. TEAS of Tianshu combined with arms' SSR demonstrated a latency of (1 519.36±206.99) ms and a voltage amplitude of (0.66±0.34) mV; for the legs, latency was (2 004.80±508.53) ms and voltage amplitude was (0.55±0.28) mV. In the distal gastrectomy without nerve preservation group, TEAS of Zusanli combined with arms' SSR revealed a latency of (2 385.95±710.27) ms and a voltage amplitude of (0.23±0.11) mV; for the legs, latency was (2 506.81±779.37) ms and voltage amplitude was (0.26±1.29) mV. TEAS of Tianshu combined with arms' SSR indicated a latency of (2 697.78±385.55) ms and a voltage amplitude of (0.21±0.14) mV; for the legs, latency was (2 949.14±506.61) ms and voltage amplitude was (0.17±0.11) mV. The group without nerve preservation exhibited significantly prolonged latencies and reduced voltage amplitudes (all P<0.01). No statistically significant differences were observed between the groups in operative time, intraoperative bleeding, the number of dissected lymph nodes, inflammatory indicators (IL-6, CRP, PCT) at 3 days postoperatively, or anastomotic leakage rates (all P>0.05). In the group without nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.36±0.58), (1.04±0.97), and (1.74±1.10) times/min, respectively, with bowel function recovery time of (62.24±9.91) hours. The PNI at 3 months postoperatively was (37.42±3.01). Incidences of food residue in the residual stomach and bile reflux were 21.79% (17/78) and 29.49% (23/78), respectively. In the group with nerve preservation, bowel sounds on postoperative days 1, 2, and 3 were (0.76±0.82), (2.03±1.34), and (3.71±1.27) times/min, respectively, with bowel function recovery time of (44.94±8.05) hours. The PNI at 3 months postoperatively was (41.34±3.40). Incidences of food residue and bile reflux were 5.88% (2/34) and 11.76% (4/34), respectively. Statistically significant differences were observed between the groups (all P < 0.05). Conclusion:TEAS of Zusanli and Tianshu combined with SSR provides an objective measure for assessing the preservation of perigastric autonomic nerves during radical gastrectomy.
5.Latest progress and prospect of NRP-1 targeted molecular probes for breast cancer diagnosis
Shuyue CAI ; Quan XIE ; Yuxuan ZHOU ; Qingzhu LIU ; Ling QIU ; Jianguo LIN
China Oncology 2025;35(2):249-254
Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.
6.Multimodal MRI-based neurophenotype correlated to structural bowel damage in Crohn's disease
Zhuangnian FANG ; Ruonan ZHANG ; Lili HUANG ; Xiaodi SHEN ; Qingzhu ZHENG ; Yangdi WANG ; Xuehua LI ; Zhoulei LI ; Shaochun LIN
The Journal of Practical Medicine 2025;41(15):2398-2405
Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506~0.945)in the bowel damage group and 0.155(95%CI:0.093~0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.
7.Latest progress and prospect of NRP-1 targeted molecular probes for breast cancer diagnosis
Shuyue CAI ; Quan XIE ; Yuxuan ZHOU ; Qingzhu LIU ; Ling QIU ; Jianguo LIN
China Oncology 2025;35(2):249-254
Breast cancer is one of the most prevalent malignant tumor in women worldwide,in which,triple-negative breast cancer(TNBC)is highly invasive and metastatic.In recent years,the incidence rate of TNBC has gradually increased and shown a trend of younger age.With the in-depth research on the molecular mechanism of breast cancer,neuropilin-1(NRP-1),a transmembrane protein,has been found to be associated with metastasis and prognosis of breast cancer,particularly TNBC.Therefore,NRP-1 has become a promising target for the diagnosis and treatment of breast cancer.The expression and distribution of NRP-1 in breast cancer can be detected by nuclear medicine,optical imaging and multimodal imaging methods in a non-invasive,real-time and accurate manner,which has significant application value in the early diagnosis,staging,treatment,and prognosis evaluation of breast cancer.Nuclear medicine probes specifically target tumor cells or tissues by combining radionuclides(e.g.,68Ga and 99mTc)with specific molecular ligands,and the signal is captured using positron emission tomography(PET)or single-photon emission computed tomography(SPECT),allowing for sensitive diagnosis of breast cancer.With the development of medical imaging and other interdisciplinary subjects,the NRP-1 targeted multimodal molecular probe[68Ga]Ga-NODAGA-K(Cy5)DKPPR combined the high sensitivity of PET with the high resolution advantage of near-infrared fluorescence(NIRF)to achieve precise diagnosis of breast cancer and provide real-time fluorescence navigation during surgery,enhancing the accuracy of tumor tissue identification and excision.In this paper,the advantages and disadvantages of NRP-1 targeted molecular probes in the diagnosis of breast cancer were systematically compared,and the application scope and latest research progress of various probes in the diagnosis and treatment of breast cancer were described,in order to provide reference for the development and clinical application of breast cancer targeted molecular probes.
8.Comparison of the application of double tract anastomosis and single muscular flap valvuloplasty technique in laparoscopic proximal gastrectomy for digestive tract reconstruction
Hansong FAN ; Qingzhu DING ; Huina WANG ; Zhiyi CHENG ; Chuanjiang HUANG ; Guiyuan LIU ; Xiaojun ZHAO ; Xiaolan YOU
Chinese Journal of Gastrointestinal Surgery 2025;28(11):1291-1301
Objective:To explore the clinical efficacy of double tract reconstruction and single flap valvuloplasty technique in laparoscopic proximal gastrectomy.Methods:A retrospective cohort study was adopted to analyze the clinical data of 65 patients with gastric cancer who underwent radical proximal gastrectomy at Taizhou People's Hospital Affiliated to Nanjing Medical University from July 2019 to April 2024. According to the different reconstruction methods, the patients were divided into the double tract reconstruction group (double tract; n=43) and oblique anastomosis of esophageal-gastric mucosal window with single flap valvuloplasty technique group (single flap n=22). The baseline data, surgical and postoperative recovery indicators, postoperative pathological results, gastroesophageal reflux at postoperative 6 months, and nutritional status at postoperative 1 year were compared between the two groups. Results:Comparisons of operative time, gastrointestinal reconstruction time, number of lymph nodes dissected, postoperative intestinal function recovery time, total protein, plasma albumin, hemoglobin, and lymphocyte count at 1 week postoperatively, prognostic nutritional index (PNI), time to normalization of postoperative white blood cell count and C-reactive protein, length of hospital stay, hospital costs, and incidence of postoperative pulmonary infection or anastomotic leakage between the two groups showed no statistically significant differences (all P>0.05). However, compared with the double tract group, the single muscle flap group had significantly higher intraoperative blood loss ( P<0.001), higher maximum postoperative body temperature ( P=0.004), and a significantly higher proportion of patients with pleural effusion ≥2 cm ( P=0.029).No statistically significant differences were observed between the two groups in terms of tumor length, length of esophageal involvement, Siewert classification, tumor differentiation degree, neural invasion, lymphovascular invasion, number of metastatic lymph nodes, tumor T stage and N stage, or UICC TNM staging for gastric cancer (all P>0.05). Nevertheless, the minimum distance of the lower resection margin in the double tract group was significantly longer than that in the single muscle flap group, with a statistically significant difference between the groups ( P<0.001). At 6 months postoperatively, results from the Quality of Life Questionnaire-Core 30 (QLQ-C30), Quality of Life Questionnaire-Stomach 22 (QLQ-ST022), Reflux Symptom Index scores, Visick grading, and gastroscopy (Los Angeles classification) all indicated that the incidence of reflux esophagitis in the double tract group was significantly lower than that in the single muscle flap group (all P<0.001). Gastrointestinal contrast examination showed no anastomotic stenosis in either group; gastroesophageal reflux occurred in 5 cases (11.6%) in the double tract group and 4 cases (18.2%) in the single muscle flap group, with no statistically significant difference (χ2=0.524, P=0.469). Gastroscopy results revealed that the incidence of reflux esophagitis at 6 months postoperatively was 9.3% (4/43) in the double tract group and 59.1% (13/22) in the single muscle flap group, with a statistically significant difference between the two groups (χ2=18.680, P<0.001).At 1 year postoperatively, the dual-chamber group showed better performance in body mass index(BMI), proportion of a decrease in BMI, plasma albumin, and PNI compared with the single muscle flap group, with statistically significant differences (all P<0.05). There were no statistically significant differences in hemoglobin or lymphocyte count between the two groups (all P>0.05). During 1 year of follow-up, one case of anastomotic recurrence occurred in each group, with no statistically significant difference between the groups ( P=0.624). Conclusions:Both proximal gastrectomy with double-tract anastomosis and esophagogastric mucosal window oblique anastomosis combined with single muscular flap valvuloplasty for digestive tract reconstruction are safe and feasible. However, double-tract anastomosis can better prevent the occurrence of postoperative reflux esophagitis, improve the patient's postoperative nutritional status, and enhance the patient's quality of life.
9.Multimodal MRI-based neurophenotype correlated to structural bowel damage in Crohn's disease
Zhuangnian FANG ; Ruonan ZHANG ; Lili HUANG ; Xiaodi SHEN ; Qingzhu ZHENG ; Yangdi WANG ; Xuehua LI ; Zhoulei LI ; Shaochun LIN
The Journal of Practical Medicine 2025;41(15):2398-2405
Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506~0.945)in the bowel damage group and 0.155(95%CI:0.093~0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.
10.Construction and validation of a job competency model for mental health professionals in Tianjin City
China Occupational Medicine 2025;52(1):50-55
Objective To construct and validate a competency model for mental health professionals. Methods The literature analysis method, semi-structured expert interview method and Delphi method were used to construct the job competency model of mental health professionals. The hierarchical analysis method was used to construct the judgment matrix of each index and determine its weight coefficient. A total of 23 psychiatrists were selected as the validation subjects using the convenience sampling method to validate the model's effectiveness. Results The recovery rate of the valid correspondence questionnaire in this study was 100%, with an expert authority degree of 0.823, a coefficient of variation ranging from 0.070 to 0.101, and Kendall's W of 0.627-0.763 (all P<0.001). The constructed job competency model includes five primary indicators and 38 secondary indicators. The results of the consistency test (CR) showed that the CR value of the primary indicators was 0.028, and the CR values of the secondary indicators were 0.041, 0.034, 0.015, 0.020, and 0.032. The results of the hierarchical analysis showed that the weight ranking, in descending order, for primary indicators was knowledge, skills, ethical quality, intrinsic motivation, and personal traits. The top five secondary indicator combinations with the highest weights were basic clinical medicine knowledge, mental health professional knowledge, clinical diagnosis and treatment ability, medical ethics knowledge, and dedication to the job. The results of the validation analysis showed that the model scores for the 23 psychiatrists were consistent with their annual unit assessment results. Conclusion The constructed job competency model for mental health professionals can provide a reference for training and evaluation in mental health workforce development.

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