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.

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.

Objective:To investigate the application value of magnetic resonance imaging(MRI) in evaluating the efficacy of anti-PD-1 combined with neoadjuvant therapy for microsatellite stability (MSS)/proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC).Methods:The prospective single-arm phase Ⅱ study was conducted. The clinicopathological data of 37 patients with MSS/pMMR LARC who were admitted to Beijing Friendship Hospital of Capital Medical University from April 2021 to September 2022 were collected. All patients underwent anti-PD-1 combined with neoadjuvant therapy and radical total mesorectal excision. Observation indicators: (1) enrolled pati-ents; (2) MRI and pathological examination; (3) concordance analysis of MRI examination reading; (4) evaluation of MRI examination. Measurement data with normal distribution were represented as Mean± SD. Count data were expressed as absolute numbers or percentages. Linear weighted κ value was used to evaluate the concordance of radiologist assessment. Sensitivity, negative predictive value, accuracy, overstaging rate and understaging rate were used to evaluate the predictive value. Results:(1) Enrolled patients. A total of 37 eligible patients were screened out, including 21 males and 16 females, aged (61±11)years. MRI examination was performed before and after combined therapy, and pathological examination was performed after radical resection. (2) MRI and pathological examination of patients. Among the 37 patients, MRI before combined therapy showed 0, 0, 5, 24 and 8 cases in stage T0, T1, T2, T3 and T4, 10, 17 and 10 cases in stage N0, N1 and N2, 28 and 9 cases of positive and negative extramural vascular invasion (EMVI), 4 and 33 cases of positive and negative mesorectal fascia (MRF), respectively. MRI examination after combined therapy showed 15, 4, 7, 10 and 1 cases in stage T0, T1, T2, T3 and T4, 34, 2 and 1 cases in stage N0, N1 and N2, 9 and 28 cases of positive and negative EMVI, 1 and 36 cases of positive and negative MRF. There were 16, 13, 8 and 0 cases of tumor regression grading (TRG) 0, 1, 2 and 3, respectively. Postoperative pathological examination showed 18, 4, 3, 11, 1 cases in stage T0, T1, T2, T3, T4, 33, 3, 1 cases in stage N0, N1, N2, positive and negative EMVI and unknown data in 1, 35, 1 cases, positive and negative circumferential margin in 0 and 37 cases, grade 0, grade 1, grade 2, grade 3 of American Joint Committee on Cancer TRG in 18, 9, 8, 2 cases, respectively. Pathological complete response rate was 48.6%(18/37) and approximate pathological complete response rate was 24.3%(9/37). (3)Concordance analysis of MRI examination reading. The κ value of T staging and N staging on MRI before combined therapy was 0.839 ( P<0.05) and 0.838 ( P<0.05), respectively. The κ value of T staging and N staging on MRI after combined therapy was 0.531 ( P<0.05) and 0.846 ( P<0.05), respectively. The κ value of EMVI and MRF was 0.708 ( P<0.05) and 0.680 ( P<0.05) before combined therapy, and they were 0.561 ( P<0.05) and 1.000 ( P<0.05) after combined therapy, respectively. The κ value of TRG 3-round reading for TRG was 0.448 ( P<0.05). (4) Evaluation of MRI examination. ① MRI evaluation of T and N staging. The accuracy of MRI examination after combined therapy for distinguishing stage T0 was 75.7%[28/37, 95% confidence interval ( CI) as 62.2%-89.2%], the understaging rate was 8.1%(3/37, 95% CI as 0-18.9%), the overstaging rate was 16.2%(6/37, 95% CI as 5.4%-29.7%). The accuracy of MRI examination for distinguishing stage T0-T2 was 86.5%(32/37, 95% CI as 73.0%-97.3%), its understaging rate and overstaging rate were 8.1%(3/37, 95% CI as 0-18.9%) and 5.4% (2/37, 95% CI as 0-13.5%), respectively. The accuracy of MRI examination for distinguishing N staging was 91.9%(34/37, 95% CI was 81.1%-100.0%), its understaging rate and overstaging rate were 5.4%(2/37, 95% CI as 0-13.5%) and 2.7%(1/37, 95% CI as 0-8.1%), respectively. Among 18 patients in pathological stage T0, the overstaging rate of MRI was 33.3%(6/18). All the 4 patients in pathological stage T1 and 3 pati-ents in pathological stage T2 had correct diagnosis. There were 3 cases with understaging among 12 patients in pathological stage T3-T4. Among the 37 patients in pathological stage N0-N2, 34 cases had correct diagnosis, 1 case was overstaged as stage N1 due to a round mesorectal lymph node with short diameter as 6 mm, and 2 cases were diagnosed as stage N0 due to the small lymph nodes with the maximum short diameter as 3 mm. ② MRI evaluation of EMVI and MRF. The accuracy, sensitivity and negative predictive value of MRI for evaluating EMVI were 86.5%(32/37, 95% CI as 75.0%-97.2%), 100.0% and 100.0%, respectively, and the overestimation rate of EMVI was 13.9%(5/36, 95% CI as 2.8%-25.0%), and no underestimation occurred. Of 35 pathologically negative EMVI patients, a rate of 14.3%(5/35) of patients were positive on MRI. The main reason for overestaging was that thickened fibrous tissue outside the rectal wall was mistaken for vascular invasion. The accuracy of MRI for evaluating MRF was 97.3%(36/37, 95% CI as 91.9%-100.0%), and 1 case (1/37, 2.7%, 95% CI as 0-8.1%) was overestimated as positive MRF due to misdiagnosis of pararectal MRF lymph nodes. The negative predictive value of MRI for assessing MRF was 100.0%. ③ MRI evaluation of TRG. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0 were 78.4%(29/37, 95% CI as 64.9%-91.9%), 8.1%(3/37, 95% CI as 0-18.9%), 13.5%(5/37, 95% CI as 5.4%-27.0%), respectively. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0-1 were 89.2%(33/37, 95% CI as 78.4%-97.3%), 8.1%(3/37, 95% CI as 0-18.9%), 2.7%(1/37, 95% CI as 0-8.1%), respectively. Of the 18 patients with pathologic complete response, 5 cases were diagnosed as pathological TRG 1 and 13 cases as pathological TRG 0. One near-pCR patient was assessed as pathological TRG 2. Two patients with pathological TRG 3 were incorrectly diagnosed on MRI. Conclusions:Anti-PD-1 combined with neoadjuvant therapy can downstage the LARC pati-ents with MSS/pMMR. MRI is effective in predicting T staging, N staging, EMVI, MRF and TRG. However, overstaging should be prevented.

【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To evaluate the predictive value of preoperative frailty combined with nutritional status for prolonged postoperative ileus (PPOI) in the patients with gynecological malignancies.Methods:Patients undergoing elective surgery for gynecological malignancies in the Affiliated Hospital of Jiangnan University from April 2022 to February 2023 were selected. The Frail scale was used to evaluate the frailty within 24 h of admission, and the nutritional status was evaluated by the Controlling Nutritional Status score. The general characteristics of patients and occurrence of PPOI were recorded, and the risk factors for PPOI were analyzed by multivariate logistic regression. The ability of frailty, nutritional status and their combination to predict PPOI was assessed by the receiver operating characteristic curve.Results:Two hundred and fourteen patients were finally included, 52 cases developed of PPOI, and 98 cases were frail patients. Preoperative frailty combined with moderate to severe malnutrition was an independent risk factor for PPOI in the patients with gynecological malignancies ( P<0.05), and the area under the curve in predicting the occurrence of PPOI was 0.796 (95% confidence interval 0.736-0.857) in the patients with gynecological malignancies. Conclusions:Preoperative frailty combined with moderate to severe malnutrition has a higher accuracy in predicting PPOI in the patients with gynecological malignancies.

Objective:To investigate the clinical outcome of transposition of the medial gastrocnemius muscle flap in repairing the middle and upper tibial soft tissue defects.Methods:The clinical data of patients with mid-upper tibial tissue defects admitted to the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from September 2016 to June 2020 were retrospectively analyzed. Doppler ultrasound was used to detect and mark the blood vessels and branches of the lower limbs before surgery, the medial gastrocnemius muscle flap was designed according to the wound condition of the patient, the soft tissue defects in the middle and upper part of the tibia were repaired by transposition, and the appearance, color, feel, texture, gait and plantar flexion strength of the affected foot, as well as the recovery of the donor site were followed up after surgery. For patients with chronic osteomyelitis, the efficacy is evaluated with reference to McKee and other osteomyelitis treatment standards, including three levels: cure, improvement and recurrence.Results:A total of 11 patients were enrolled, including 9 males and 2 females, aged 48 to 69 years. The area of soft tissue defect ranged 3.8 cm×5.7 cm-14.2 cm×7.6 cm, and the flap size ranged 13.0 cm×6.0 cm-21.0 cm×13.0 cm. After surgery, one case had blisters at the distal end, which were cured after conservative measures. Other flaps and donor wounds presented good blood circulation, the shape and function recovered satisfactorily, and the incision healed uneventfully. 11 cases were followed up for 7-18 months after surgery, with an average of 13.2 months, and the appearance, color and texture of the flap were basically satisfactory. The two-point distance perception of the flap was 13-20 mm 9 months after surgery, with an average of 15 mm. At the last follow-up visit, the plantar flexion strength of the affected side was weaker than that of the healthy side, but the gait was basically normal. All 4 patients with chronic osteomyelitis met the clinical cure criteria, and there was no rash, swelling, overheat and pain, rupture, exudation and sinus tract formation at the primary lesion during the follow-up period (average 14 months), and no osteosclerosis and dead bone formation were found on X-ray examination. There was no deformity and dysfunction at the donor site. There was one case presented pigmentation at the donor site of the thigh. Some cases presented superficial scarring.Conclusions:The transposition of the medial gastrocnemius muscle flap repairs the middle and upper tibial tissue defects without sacrificing the major blood vessels, and the flap survival rate is high, the complications are minimal, and the function and morphological recovery of the receiving area are good.

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

Objective:To investigate the clinical outcome of transposition of the medial gastrocnemius muscle flap in repairing the middle and upper tibial soft tissue defects.Methods:The clinical data of patients with mid-upper tibial tissue defects admitted to the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from September 2016 to June 2020 were retrospectively analyzed. Doppler ultrasound was used to detect and mark the blood vessels and branches of the lower limbs before surgery, the medial gastrocnemius muscle flap was designed according to the wound condition of the patient, the soft tissue defects in the middle and upper part of the tibia were repaired by transposition, and the appearance, color, feel, texture, gait and plantar flexion strength of the affected foot, as well as the recovery of the donor site were followed up after surgery. For patients with chronic osteomyelitis, the efficacy is evaluated with reference to McKee and other osteomyelitis treatment standards, including three levels: cure, improvement and recurrence.Results:A total of 11 patients were enrolled, including 9 males and 2 females, aged 48 to 69 years. The area of soft tissue defect ranged 3.8 cm×5.7 cm-14.2 cm×7.6 cm, and the flap size ranged 13.0 cm×6.0 cm-21.0 cm×13.0 cm. After surgery, one case had blisters at the distal end, which were cured after conservative measures. Other flaps and donor wounds presented good blood circulation, the shape and function recovered satisfactorily, and the incision healed uneventfully. 11 cases were followed up for 7-18 months after surgery, with an average of 13.2 months, and the appearance, color and texture of the flap were basically satisfactory. The two-point distance perception of the flap was 13-20 mm 9 months after surgery, with an average of 15 mm. At the last follow-up visit, the plantar flexion strength of the affected side was weaker than that of the healthy side, but the gait was basically normal. All 4 patients with chronic osteomyelitis met the clinical cure criteria, and there was no rash, swelling, overheat and pain, rupture, exudation and sinus tract formation at the primary lesion during the follow-up period (average 14 months), and no osteosclerosis and dead bone formation were found on X-ray examination. There was no deformity and dysfunction at the donor site. There was one case presented pigmentation at the donor site of the thigh. Some cases presented superficial scarring.Conclusions:The transposition of the medial gastrocnemius muscle flap repairs the middle and upper tibial tissue defects without sacrificing the major blood vessels, and the flap survival rate is high, the complications are minimal, and the function and morphological recovery of the receiving area are good.

Purpose: The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods: A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results: The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.

Purpose: The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods: A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results: The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.