OBJECTIVES: To investigate the expression of apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and its effects on proliferation and apoptosis of PTC cells. METHODS: The expression level of APOC1 in PTC and its impact on prognosis were analyzed using GEPIA 2 and Kaplan-Meier databases. Immunohistochemistry (IHC) and Western blotting were used to detect the expression of APOC1 in PTC and adjacent tissues and in 3 PTC cell lines and normal thyroid Nthyori 3-1 cells. In TPC-1 and BCPAP cells, the effect of Lipofectamine 2000-mediated transfection with APOC1 siRNA or an APOC1-overexpressing plasmid on cell growth and colony formation ability were examined by observing the growth curves and using colony-forming assay. The changes in cell cycle and apoptosis of the transfected cells were analyzed with flow cytometry. RT-qPCR and Western blotting were used to detect the changes in expressions of P21, P27, CDK4, cyclin D1, Bcl-2, Bax, caspase-3 and caspase-9 and the key proteins in the JAK2/STAT3 signaling pathway. RESULTS: APOC1 expression was significantly higher in PTC tissues and the 3 PTC cell lines than in the adjacent tissues and Nthyori 3-1 cells, respectively. In TPC-1 and BCPAP cells, APOC1 knockdown obviously reduced cell proliferative activity, increased the percentage of G0/G1 phase cells, lowered the percentages of S and G2 phase cells, promoted cell apoptosis, and downregulated mRNA and protein expression levels of CDK4, cyclin D1 and Bcl-2 and the protein levels of p-JAK2 and p-STAT3. APOC1 overexpression in the cells produced the opposite effects on cell proliferation, apoptosis, cell cycle and the mRNA and protein expressions. The application of AG490, a JAK2 inhibitor, strongly attenuated APOC1 overexpression-induced activation of the JAK2/STAT3 signaling pathway in BCPAP cells. CONCLUSIONS APOC1 overexpression promotes proliferation and inhibits apoptosis of PTC cells possibly by activating the JAK2/STAT3 signaling pathway and accelerating cell cycle progression.
Humans ; Apoptosis ; Cell Proliferation ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Janus Kinase 2/metabolism* ; Thyroid Neoplasms/pathology* ; Thyroid Cancer, Papillary ; Cell Line, Tumor ; Carcinoma, Papillary

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Objective:To investigate the effect of abdominal circumference on intestinal radiation dose volume and acute intestinal toxicity in pelvic intensity modulated radiation therapy for rectal cancer.Methods:A total of 150 patients with locally advanced rectal cancer (LARC) who received adjuvant and neoadjuvant concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guizhou Medical University from March 2023 to January 2025 were enrolled, including 82 cases of adjuvant radiotherapy and 68 cases of neoadjuvant radiotherapy. All patients underwent radiotherapy CT simulation positioning in the standard mode of prone position with abdominal board padding and bladder filling. Intestinal toxicity was categorized as a binary variable based on the occurrence of ≥2 grade acute intestinal toxicity. Linear and logistic regression models were used to analyze the factors influencing intestinal radiation dose volumes (V 10, V 20, V 30, V 40) and acute intestinal toxicity in LARC patients. Generalized additive models and piecewise linear and logistic regression analyses were employed to examine the threshold effects of abdominal circumference on intestinal radiation dose volumes and acute intestinal toxicity. The threshold value for abdominal circumference was determined based on the upper limit of the 95% CI for the threshold. A difference test was used to validate the differences in intestinal radiation dose volume and acute intestinal toxicity between small and medium-to-large abdominal circumferences. Results:Univariate analysis showed that, gender, body mass, abdominal circumference, planning target volume (PTV), intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, abdominal circumference, intestinal volume were all influencing factors for the radiation dose volumes (V 10, V 20, V 30, V 40) of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Body mass index (BMI), abdominal circumference, intestinal volume and individual intestinal radiation volumes (V 10, V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy (all P<0.05). Body mass, BMI, abdominal circumference, multiple intestinal radiation dose volumes (V 20, V 30, V 40) were all influencing factors for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy (all P<0.05). Multivariate analysis showed that, abdominal circumference (V 10: β=-1.01, 95% CI: -1.68--0.33, P=0.004; V 20: β=-0.94, 95% CI: -1.28--0.60, P<0.001; V 30: β=-0.58, 95% CI: -0.82--0.34, P<0.001; V 40: β=-0.41, 95% CI: -0.60--0.23, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference (V 10: β=-0.92, 95% CI: -1.62--0.22, P=0.010; V 20: β=-0.84, 95% CI: -1.11--0.57, P<0.001; V 30: β=-0.42, 95% CI: -0.57--0.28, P<0.001; V 40: β=-0.30, 95% CI: -0.41--0.19, P<0.001) was an independent influencing factor for the radiation dose volume of each intestinal segment of patients with LARC undergoing neoadjuvant radiotherapy. Abdominal circumference ( OR=0.86, 95% CI: 0.78-0.95, P=0.002) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing adjuvant radiotherapy. Abdominal circumference ( OR=0.87, 95% CI: 0.79-0.96, P=0.004) was an independent influencing factor for the acute intestinal toxicity of patients with LARC undergoing neoadjuvant radiotherapy. The generalized additive model revealed a nonlinear relationship between abdominal circumference and intestinal radiation dose volume and acute intestinal toxicity of adjuvant radiotherapy patients. Further segmented regression analysis results showed that there was a threshold effect between abdominal circumference and intestinal radiation dose volume (V 10, V 20, V 30, V 40) and acute intestinal toxicity. The inflection point values between abdominal circumference and intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing adjuvant radiotherapy were all 71.9 cm; the inflection point values between abdominal circumference and the intestinal radiation dose volume V 10, V 20, V 30, V 40 in LARC patients undergoing neoadjuvant radiotherapy were 69.0, 69.0, 69.0, 68.6 cm, respectively; The inflection point values between abdominal circumference and acute intestinal toxicity in LARC patients undergoing adjuvant radiotherapy and neoadjuvant radiotherapy were 71.9, 69.0 cm, respectively. Based on the upper limit of the 95% CI threshold, the cutoff values for small and medium-to-large abdominal circumferences for patients undergoing adjuvant and neoadjuvant radiotherapy were set at 76.1, 71.9 cm, respectively. In patients undergoing adjuvant radiotherapy, the levels of intestinal radiation dose volume V 10 [ (7.65±2.29) cm 3vs. (5.88±2.68) cm 3, t=2.76, P=0.007], V 20 [ (4.28±1.27) cm 3vs. (2.72±1.31) cm 3, t=4.81, P<0.001], V 30 [ (2.42±1.07) cm 3vs. (1.37±0.76) cm 3, t=4.95, P<0.001], V 40 [ (1.69±0.74) cm 3vs. (0.92±0.58) cm 3, t=4.93, P<0.001] in the small abdominal circumference group ( n=22) were significantly higher than those in patients with medium-to-large abdominal circumferences ( n=60) ; In patients undergoing neoadjuvant radiotherapy, patients with small abdominal circumferences ( n=11) had significantly higher V 20 [ (3.09±0.84) cm 3vs. (2.28±1.17) cm 3, t=2.17, P=0.033], V 30 [1.44 (1.22, 1.53) cm 3vs. 0.91 (0.56, 1.22) cm 3, Z=-3.04, P=0.002], V 40 [0.93 (0.84, 1.09) cm 3vs. 0.44 (0.30, 0.81) cm 3, Z=-3.19, P=0.001] than patients with medium-to-large abdominal circumferences ( n=57). In patients receiving adjuvant radiotherapy and neoadjuvant radiotherapy, there were statistically significant differences in acute intestinal toxicity between patients with small abdominal circumferences and with medium-to-large abdominal circumferences ( χ2=10.46, P=0.001; χ2=8.13, P=0.004) . Conclusions:In the standard mode (prone position with abdominal board padding and bladder filling), abdominal circumference is an independent factor influencing the intestinal radiation dose volume and acute intestinal toxicity in rectal cancer radiotherapy patients. There is a significant non-linear threshold effect between abdominal circumference and different levels of intestinal radiation dose volume and acute intestinal toxicity. The impact of abdominal circumference on intestinal radiation dose volume and toxicity differs significantly before and after the inflection point value. Patients with smaller abdominal circumferences not only fail to achieve the expected benefits under the current standard radiotherapy regimen but also face higher risks of intestinal radiation dose volume and toxicity.

Objective:To explore the effective indicators that can predict the poor prognosis of neonates with congenital heart disease after surgery.Methods:178 cases of neonatal congenital heart disease were retrospectively analyzed. According to the outcome, they were divided into normal prognosis group (132 cases) and poor prognosis group (46 cases).Results:15 (8.4%) patients died in hospital. There were statistical differences between the two groups in terms of whether PGE and vasoactive drugs were needed before surgery, preoperative respiratory support mode, blood lactate level from anesthesia induction to 24 h after surgery, VIS and VVR scores, whether delayed sternal closure or peritoneal dialysis were needed ( P<0.05). Logistic regression analysis showed that elevated lactate levels and VVR scores on 24 h after surgery were independent risk factors for death or other poor postoperative prognosis in neonates ( P<0.05). Conclusion:The levels of lactate and VVR scores in 24 h after operation are sensitive indicators for monitoring the severity of the condition, guiding treatment and judging prognosis of neonatal congenital heart disease surgery.

Objective To explore the clinical features and treatments of Chinese patients with bullous pemphigoid (BP) induced by immune checkpoint inhibitors (ICI). Methods A retrospective analysis was conducted on 18 Chinese patients with ICI-induced BP treated in the Peking Union Medical College Hospital and 14 Chinese patients with this disease reported in the literature.Furthermore,the research data of non-Chinese patients were used for comparison to outline the clinical features and treatment responses of the Chinese patients. Results A total of 32 patients (21 males and 11 females) were enrolled,and all of them presented BP induced by programmed death-1/programmed death ligand-1 inhibitors.Compared with non-Chinese patients,the Chinese patients with ICI-induced BP showed low average ages [(65.2±9.5) years vs. (69.9±10.3) years,P=0.020],increased proportion of BP induced by tislelizumab (28.1% vs. 0,P<0.001),decreased proportions of BP induced by pembrolizumab (18.8% vs. 39.4%,P=0.029) and nivolumab (3.1% vs. 52.8%,P<0.001),and decreased proportion of primary malignant melanoma (9.4% vs. 43.3%,P<0.001).The incidence of pruritus (96.9% vs. 66.1%,P<0.001) and mucosal involvement (59.4% vs. 15.7%,P<0.001) in the Chinese patients were higher than those in the non-Chinese patients.The proportions of the Chinese patients treated with tripterygium glycosides (9.4% vs. 0,P=0.008),dupilumab (18.8% vs. 0.8%,P<0.001),and topical corticosteroids (87.5% vs. 53.5%,P<0.001) were higher than those of non-Chinese patients. Conclusions The Chinese patients with ICI-induced BP tend to have a younger age and a higher probability of BP induced by tislelizumab than the non-Chinese patients.Unlike that in the non-Chinese patients,the primary tumor in the Chinese patients with ICI-induced BP is predominantly lung cancer.Pruritus is more obvious,and mucosal involvement is more common in the Chinese patients.Systemic corticosteroid therapy is the international standard treatment for ICI-induced BP,while tripterygium glycosides and dupilumab are characteristic therapies in China.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Antibodies, Monoclonal, Humanized/therapeutic use* ; East Asian People ; Immune Checkpoint Inhibitors/adverse effects* ; Pemphigoid, Bullous/chemically induced* ; Retrospective Studies

Objective To investigate the viability of Runt-related transcription factor 1(RUNX1)as a biomarker for gastric cancer and to assess the impact of the small molecule inhibitor Ro24-7429 on the proliferation,migration,and invasion of gastric cancer cells following targeted modulation.Methods Through the GEPIA database,we analyzed RUNX1 mRNA expression in gastric cancer or normal gastric tissues.Utilizing RUNX1 expression data from the TCGA database,a receiver operating characteristic(ROC)curve was constructed to appraise the potential of RUNX1 as a gastric cancer biomarker.In September 2022,we collected tissue samples from 6 patients with gastric cancer from the Department of General Surgery at the Second Hospital of Lanzhou University.After extracting tissue proteins,Western blotting was employed to compare RUNX1 protein expression in tumor and adjacent tissues.Gastric cancer cell lines with high RUNX1 expression were identified and the suppressive effect of the small molecule inhibitor Ro24-7429 on RUNX1 protein expression was verified by Western blotting.the effect of Ro24-7429 was validated by using CCK-8,colony formation,cell scratch,and Transwell assays.RUNX1 protein levels in gastric cancer tissues were quantified using immunohistochemical staining.An organoid model of gastric cancer was then established from the high-expression samples and verified by both HE and immunization analyses.Lastly,the impact of Ro24-7429 on the growth of gastric cancer organoids with meticulous tracking was evaluated using a biological microscope within a designated area.Results The analysis from the GEPIA database revealed a heightened expression of RUNX1 mRNA in gastric cancer tissues compared with normal tissues(P<0.05).The ROC curve derived from the RUNX1 expression data in the TCGA database boasts an area under the curve(AUC)of 0.956,underscoring RUNX1's potential as a robust diagnostic marker.Western blotting results revealed significantly higher RUNX1 protein expression in gastric cancer tissues than in adjacent tissues(P<0.001).Among 5 gastric cancer cell lines studied,AGS and HGC27 exhibited pronounced RUNX1 protein expression(P<0.001).The small molecule inhibitor Ro24-7429,targeting RUNX1,potently suppressed RUNX1 expression in gastric cancer cells.The results from CCK-8,colony formation,scratch,and Transwell assays showed that Ro24-7429 effectively inhibited proliferation,migration,and invasion of gastric cancer cells(P<0.001).In a gastric cancer organoid model derived from high RUNX1 expression samples,the RUNX1 expression was remarkably consistent with its originating tissue.As expected,upon the targeted inhibition of RUNX1 using Ro24-7429,the cancer organoids significantly reduced growth capacity.Conclusions RUNX1 shows potential as a biomarker for gastric cancer.Ro24-7429 specifically inhibits RUNX1 expression and suppresses tumor cell proliferation,migration,and invasion in gastric cancer cell lines and organoid models.

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.
Female ; Humans ; Urinary Bladder/surgery* ; Ureter/surgery* ; Rectus Abdominis ; Drainage ; Fistula

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.
Female ; Humans ; Urinary Bladder/surgery* ; Ureter/surgery* ; Rectus Abdominis ; Drainage ; Fistula

Objective:To summarize the effect of one and a half ventricle repair in the treatment of Ebstein’s Anomaly.Methods:The data of 149 patients diagnosed with Ebstein’s Anomaly and received with surgical treatment in Pediatric Cardiac Surgery Department of Beijing Anzhen Hospital affiliated to Capital Medical University from January 2010 to December 2018 were continuously collected, and the survival rate, reoperation rate and tricuspid regurgitation were followed up in the medium-long term.Results:There were 68 males and 81 females, with a median age of 5.58 years. Patients were divided into Biventricular repair group and one and a half ventricle repair group. The operative age was significantly younger in the one and a half ventricle repair group (4.15 years vs. 6.71 years, P=0.019). There were also significant differences in patiens’ body length[(107.70±31.28)cm vs. (123.20±35.22)cm, P=0.014]and body weight[(19.69±12.22)kg vs. (29.65±20.41)kg, P=0.001], between the two groups, which may be related to the severity of the disease and the need for early surgical intervention. However, there was no significant difference between the two groups in preoperative cyanosis, hemoglobin level, cardiac function, arrhythmia, and common cardiac malformations such as atrial septal defect. Notably, the proportion of preoperatively complicated pulmonary stenosis (10.81% vs. 1.79%, P=0.016) and right ventricular dysplasia (16.22% vs. 3.57%, P=0.008) was significantly higher in the one and a half ventricle repair group. In intraoperative and postoperative indicators, as one and a half ventricle repair under the collateral circulation, extracorporeal circulation time was slightly longer [(125.51±37.35)min vs. (100.44±25.24)min, P<0.001], and other indicators such as aortic cross-clamp time, endotracheal intubation time, length of hospital stay, and mid-term follow-up results, including mid-term mortality, reoperation rate, cardiac function and valvular regurgitation, there was no significant difference between the two groups. However, the proportion of hospital mortality in half ventricular therapy group was slightly higher, which may be related to the poor right heart function and postoperative recovery difficulties. Conclusion:Good follow-up results have been achieved in the treatment of two surgical therapy. Patients with right ventricular dysplasia and pulmonary artery stenosis should be paid more attention to. Pulmonary artery pressure and pulmonary vascular development should be evaluated before surgery to make preparations for one and a half ventricle repair.