ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.

To investigate the risk factors for early relapse after curative resection of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction (AEG) and construct a visual predictive model.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.

Objective To explore the relationship between the distribution characteristics and the habitat factors of the invasive B. straminea in South China. Methods From October 2016 to August 2017, the breeding condition and habitat factors of B. straminea were investigated in the rivers of Shenzhen and its adjacent areas in the dry season, normal season and wet reason. The generalized additive model (GAM) was used to study the main habitat factors affecting the distribution density of B. straminea. Results The distribution characteristics of B. straminea showed obvious aggregation and unevenness in space. In terms of time, the density of snails was the highest in the dry season, followed by the normal water season and the least in the wet season. The GAM model analysis showed that the main habitat factors affecting the distribution density of B. straminea were water depth, water temperature, flow velocity, dissolved oxygen, and total phosphorus. When the flow velocity and water temperature were 0.25 m / s and 26 °C, respectively, the largest distribution density of snails might appear. The distribution density of B. straminea was positively correlated with dissolved oxygen and total phosphorus. Conclusion B. straminea is suitable to live in the water environment with poor water quality. In the future, the monitoring should be strengthened to provide reference for the prevention and control of the spread of the snails.

OBJECTIVE To study different extraction fractions of Agrimonia pilosa against h epatic fibrosis. METHODS Using hepatic stellate cells HSC-T 6 of rats as objects ，the effects of different extraction fractions （total extract ，ethyl acetate fraction ， petroleum ether fraction and n-butanol fraction ）with different concentrations （0.5，5，50，500，5 000 μg/mL，calculated by raw drug）of A. pilosa on the proliferation of HSC-T 6 cells were detected （after treated for 24，48，72 h）；median inhibition concentration（IC50）was also caculated. Platelet-derived growth factor （PDGF-BB）was used to induce the activation of HSC-T 6 cells to establish hepatic fibrosis cell model. Flow cytometry was used to detect the effects of different extraction fractions of A. pilosa on apoptosis of HSC-T 6 cells. The expression of collagen Ⅰ（Col-Ⅰ）in the supernatant was detected by enzyme linked immunosorbent assay. The expressions of α-smooth muscle actin （α-SMA），Col-Ⅰ，B-cell lymphoma- 2（Bcl-2），Bcl-2-associated X protein （Bax）and caspase- 3 were detected by Western blot assay. RESULTS Total extract ，ethyl acetate fraction ，petroleum ether fraction and n-butanol fraction of A. pilosa could significantly increase the apoptotic rate of HSC-T 6 cells（P＜0.01）. After treated for 24 h，IC50 of above fractions were 50.17，20.75，5.82，4.09 μg/mL，respectively. After intervened with PDGF-BB ，the expression of Col- Ⅰ in supernatant of HSC-T 6 cells as well as protein expression of Col- Ⅰ，α-SMA，Bcl-2，Bax and caspase- 3 in HSC-T6 cells were increased significantly （P＜0.01）. After intervened with different extraction fractions of A. pilosa ，most of the expressions of above proteins in HSC-T 6 cell culture supernatant or cells were significantly reversed compared with PDGF-BB group （P＜0.05 or P＜0.01）， and the intervention effect of n-butanol fraction of A. pilosa was the most significant. CONCLUSIONS Different extraction fractions of A. pilosa can inhibite the proliferation of HSC-T 6 cells and induce their apoptosis；n-butanol fraction from A. pilosa may be an effective fraction to exert the effect of anti-hepatic fibrosis.

Objective:To investigate the clinical outcomes of patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection.Methods:Patients who undergoing radical surgical resection for ICC from Jan 2015 to Apr 2021 at the Department of General Surgery, the First Affiliated Hospital of Anhui Medical University were included in this retrospective cohort study.Results:There were 67 patients in the final analysis, The median follow-up duration was 14 months (range: 1-60 months). Firty three patients (79.1%) had tumor recurrence, 52 patients (77.6%) died, Among them, 49 patients (73.1%) died from tumor recurrence. The 1-、2-、and 3-year accumulated disease-free and overall survival rate were 35.6%, 19.6%, 16.8% and 53.7%, 32.4%, 20.8%. respectively. The overall survival rate of the group without microvascular invasion was significantly better than those of the group with microvascular invasion ( χ2=5.916, P=0.015). CA19-9≥1 000 U/ml was the only independent risk factor for the disease-free survival. CA19-9≥1 000 U/ml、blood loss≥600 ml、microvascular invasion and tumor recurrence were the independent risk factors for the overall survival. Conclusion:For ICC patients with single tumor, when the tumor diameter is less than 5 cm and has no microvascular invasion, surgical resection is recommended, and a satisfactory prognosis could be achieved.

Objective:To evaluate the value of modified gastroscopic laryngeal mask airway (LMA) for airway management under general anesthesia in the patients with liver cirrhosis undergoing endoscopic esophageal variceal ligation (EVL).Methods:Sixty-two American Society of Anesthesiologists physical status Ⅱor Ⅲ patients with liver cirrhosis of either sex, aged 25-64 yr, with body mass index of 18-30 kg/m 2, undergoing endoscopic EVL with general anesthesia, were divided into 2 groups ( n=31 each) using a random number table method: tracheal tube group (group T) and modified gastroscopic LMA group (group L). After induction of anesthesia, a tracheal tube was inserted in group T, and a modified gastroscopic LMA was inserted and the patients were mechanically ventilated to maintain P ETCO 2 at 30-40 mmHg in group L. Successful tracheal intubation or insertion of modified gastroscopic LMA, successful ligator insertion and duration of ligator insertion were recorded.The occurrence of intraoperative hypotension, bradycardia and hypoxemia and consumption of propofol and remifentanil were recorded.At 1 min after tracheal intubation or right placement of LMA (T 1), immediately after the ligator insertion (T 2) and at the end of operation (T 3), Peak (P peak) and mean (P mean) airway pressure were monitored, and airway leak pressure in group L was measured.The extubation time, duration of post-anesthesia care unit stay and bucking during extubation were recorded.The occurrence of sore throat and nausea and vomiting was recorded within 6 h after operation.Postoperative satisfaction scores of endoscopists and patients were also recorded. Results:Sixty-one patients were finally enrolled in the study, with 31 in group T and 30 in group L. Compared with group T, no significant changes were found in the success rate of tracheal intubation or LMA placement, success rate of ligator insertion, P mean at each time point, incidence of postoperative nausea and vomiting, and postoperative satisfaction score of endoscopists ( P>0.05), duration of the ligator insertion was significantly shortened, P peak at each time point was decreased, the incidence of intraoperative hypotension and bradycardia was decreased, the consumption of propofol and remifentanil was reduced, the incidence of bucking during extubation and postoperative sore throat was reduced, and extubation time and duration of post-anesthesia care unit stay was shortened, and satisfaction scores of patients were increased in group L ( P<0.05). No hypoxemia was found in two groups.Airway leak pressure was maintained at 24-26 cmH 2O at each time point in group L. Conclusions:Modified gastroscopic LMA can be safely and effectively used for airway management under general anesthesia in the patients with liver cirrhosis undergoing EVL.

Objective:To identify the causative genes of sporadic thoracic aortic aneurysm or dissection (TAAD) and their correlation with clinical phenotype in the southern Chinese.Methods:We analyzed 11 core genes of TAAD probands without specific family history of 226 cases by next-generation sequencing technology, and performed sanger sequencing for their close relatives. Clinical data of each patient, including age of onset, syndromic phenotypes, involvement of aortic root, aortic maximum diameter and D-dimer were collected. And statistical software SPSS was used to evaluate the correlation between clinical phenotypes and gene mutations.Results:A total of 106 variants were detected in 226 probands with gene-positive frequency of 44.69%, consist of 16 pathogenic (P) variants, 18 likely pathogenic (LP) variants and 71 variants of uncertain significance (VUS). More than half of the mutations were from the non-syndromic TAAD, in which the FBN1 still was the most common causative gene. Earlier age of onset, an increase of women, larger diameter of aorta, Stanford B dissection and severe aortic regurgitation were likely to occur on carriers of P/LP, while thoracic aortic aneurysm occurs on carriers of VUS. Phenotype of both syndrome and dissection with aneurysm could increase the likelihood of carrying gene mutation, but D-dimer and involvement of aortic root couldn’t.Conclusion:Patients with sporadic aortic diseases in southern China have significant genetic heterogeneity and specific correlation between their clinical phenotype and gene mutation, especially in non-syndromic population. Earlier age of onset in carriers of FBN1 or ACTA2 genes, and larger maximum diameters of aorta in carrier of P/LP.