Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Benign biliary strictures are frequently encountered after liver transplantation or as a result of iatrogenic injury, among others. Complex and refractory benign biliary obstructions refer to biliary strictures that persist or treatment fails despite multiple endoscopic therapies. Traditional endoscopic approaches demonstrate suboptimal therapeutic effects in treating such patients, with a high recurrence rate. Moreover, surgical operations are highly invasive, and the outcomes are also unsatisfactory. The magnetic dilation technology establishes an external drainage sinus tract via percutaneous transhepatic biliary drainage and positions a magnet above the obstructed biliary tract; through endoscopic retrograde cholangiopancreatography, another magnet is placed beneath the obstructed biliary tract. The two magnets mutually attract each other, exerting pressure on the scar tissue in the middle of the magnets, causing it to gradually become ischemic, necrotic, and detached, and subsequently discharged along with the magnets. The biliary epithelial cells surrounding the magnets gradually repair and heal, ultimately forming a new patent anastomosis. The magnetic dilation technology, through slow compression, realizes the concurrent process of “removing” scars and healing, avoiding severe local inflammatory responses and excessive tissue hyperplasia. Consequently, the magnetic dilation technology possesses advantages such as minimally invasiveness and reliable effects, gradually emerging as an effective modality for treating complex and refractory benign biliary stricture cases.

Objective:To investigate the treatment approaches and outcomes of early hepatic artery thrombosis (E-HAT) in adult recipients following orthotopic liver transplantation (OLT).Methods:A retrospective analysis was conducted on clinical data of E-HAT cases after adult OLT at the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to June 2022. Clinical characteristics, treatment methods, therapeutic outcomes, long-term survival of recipients and grafts, and the incidence of long-term complications were summarized. The Kaplan-Meier method was utilized to calculate recipient survival rates.Results:Among 1 016 OLT recipients, 22 cases (2.2%) developed postoperative E-HAT. There were 19 males and 3 females, with a age of 44.81±9.98 years. E-HAT was diagnosed via angiography at a median of 3.5 (1.0, 7.0) days post-OLT. Twenty recipients underwent vascular intervention therapy, achieving clinical success in 14 cases (70.0%) with a mean thrombolysis duration of 5.1±3.2 days. Twelve cases (60.0%) experienced complications, including abdominal bleeding (10 cases), gastrointestinal bleeding (1 case), catheter-related infection (1 case), subcutaneous bleeding (1 case), and hepatic artery dissection (1 case). Five recipients underwent hepatic artery re-anastomosis, including two initial cases and three following failed interventional therapy. Surgery was performed at a median of 5.0 (1.0, 15.3) days post OLT, with 4 successful cases. Through combined interventional and surgical treatment, 81.8% (18/22) of grafts were salvaged. However, the success rate was significantly lower in cases with marked transaminase (AST, ALT) and total bilirubin elevation (16/18 vs 2/4). Nineteen E-HAT survivors were followed for a median of 22 (5, 52) months. During follow-up, 2 cases experienced thrombus recurrence, and 12 cases developed biliary complications, including ischemic biliary stenosis (11 cases), extensive liver necrosis (1 case), localized liver abscess (1 case), and biliary anastomotic stenosis (1 case). Seven recipients died due to graft failure. The 1-year, 3-year and 5-year cumulative survival rates were 67.2%, 60.5% and 34.5%, respectively.Conclusions:Combined interventional and surgical treatment demonstrates a high success rate for managing E-HAT, particularly when addressed before significant graft damage. Ischemic biliary stenosis remains the most common long-term complication.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Benign biliary strictures are frequently encountered after liver transplantation or as a result of iatrogenic injury, among others. Complex and refractory benign biliary obstructions refer to biliary strictures that persist or treatment fails despite multiple endoscopic therapies. Traditional endoscopic approaches demonstrate suboptimal therapeutic effects in treating such patients, with a high recurrence rate. Moreover, surgical operations are highly invasive, and the outcomes are also unsatisfactory. The magnetic dilation technology establishes an external drainage sinus tract via percutaneous transhepatic biliary drainage and positions a magnet above the obstructed biliary tract; through endoscopic retrograde cholangiopancreatography, another magnet is placed beneath the obstructed biliary tract. The two magnets mutually attract each other, exerting pressure on the scar tissue in the middle of the magnets, causing it to gradually become ischemic, necrotic, and detached, and subsequently discharged along with the magnets. The biliary epithelial cells surrounding the magnets gradually repair and heal, ultimately forming a new patent anastomosis. The magnetic dilation technology, through slow compression, realizes the concurrent process of “removing” scars and healing, avoiding severe local inflammatory responses and excessive tissue hyperplasia. Consequently, the magnetic dilation technology possesses advantages such as minimally invasiveness and reliable effects, gradually emerging as an effective modality for treating complex and refractory benign biliary stricture cases.

Objective:To investigate the treatment approaches and outcomes of early hepatic artery thrombosis (E-HAT) in adult recipients following orthotopic liver transplantation (OLT).Methods:A retrospective analysis was conducted on clinical data of E-HAT cases after adult OLT at the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to June 2022. Clinical characteristics, treatment methods, therapeutic outcomes, long-term survival of recipients and grafts, and the incidence of long-term complications were summarized. The Kaplan-Meier method was utilized to calculate recipient survival rates.Results:Among 1 016 OLT recipients, 22 cases (2.2%) developed postoperative E-HAT. There were 19 males and 3 females, with a age of 44.81±9.98 years. E-HAT was diagnosed via angiography at a median of 3.5 (1.0, 7.0) days post-OLT. Twenty recipients underwent vascular intervention therapy, achieving clinical success in 14 cases (70.0%) with a mean thrombolysis duration of 5.1±3.2 days. Twelve cases (60.0%) experienced complications, including abdominal bleeding (10 cases), gastrointestinal bleeding (1 case), catheter-related infection (1 case), subcutaneous bleeding (1 case), and hepatic artery dissection (1 case). Five recipients underwent hepatic artery re-anastomosis, including two initial cases and three following failed interventional therapy. Surgery was performed at a median of 5.0 (1.0, 15.3) days post OLT, with 4 successful cases. Through combined interventional and surgical treatment, 81.8% (18/22) of grafts were salvaged. However, the success rate was significantly lower in cases with marked transaminase (AST, ALT) and total bilirubin elevation (16/18 vs 2/4). Nineteen E-HAT survivors were followed for a median of 22 (5, 52) months. During follow-up, 2 cases experienced thrombus recurrence, and 12 cases developed biliary complications, including ischemic biliary stenosis (11 cases), extensive liver necrosis (1 case), localized liver abscess (1 case), and biliary anastomotic stenosis (1 case). Seven recipients died due to graft failure. The 1-year, 3-year and 5-year cumulative survival rates were 67.2%, 60.5% and 34.5%, respectively.Conclusions:Combined interventional and surgical treatment demonstrates a high success rate for managing E-HAT, particularly when addressed before significant graft damage. Ischemic biliary stenosis remains the most common long-term complication.

Objective:To analyze the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma (HCCA).Methods:Clinical data of 72 patients with HCCA undergoing radical resection at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to January 2022 were retrospectively analyzed, including 36 males and 36 females, aged 57(47, 63) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=39) and open group ( n=33). The surgical safety, tumor radicality, postoperative recovery, complications and survival time were compared between the two groups. Results:Operative time was comparable between the two groups [(6.4±2.6) h vs. (6.3±2.4) h, P>0.05], while the intraoperative blood loss was lower in the laparoscopic group [(531.9±273.3) ml vs. (674.6±330.0) ml]. Data were also comparable between the two groups in terms of R0 resection rate [92.3% (36/39) vs. 93.9% (31/33)], the number of lymph node dissection (7.7±2.6 vs. 7.6±2.4), and the incidence of postoperative complications [20.5% (8/39) vs. 18.2% (6/33)] (all P>0.05). However, the laparoscopic group was superior to the open group in terms of postoperative analgesia time [(2.0±0.7)d vs. (2.8±0.9)d], postoperative resumption of feeding time [(1.6±0.5)d vs. (3.9±0.9)d], and postoperative hospitalization time [(8.6±1.5)d vs. (12.8±2.2)d] ( t=4.04, 8.23, 9.47, respectively, all P<0.001). Postoperative cumulative survival was comparable between the two groups ( χ2=0.50, P=0.480). Conclusion:Laparoscopic radical resection of HCCA has similar efficacy to open surgery and has the advantage of less invasiveness and enhanced recovery.

Objective To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation. Methods Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed. Results The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05). Conclusions ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.

Objective:To explore the characteristics of biliary stricture after liver transplantation (LT) under SpyGlass peroral choledochoscopy and to investigate its treatment value for difficult stricture.Method:A total of 24 patients of biliary stricture after LT at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University underwent SpyGlass examination from January 2019 to December 2020, 15.5 months (2-58 months) after surgery. The characteristics of different types of strictures and the selective guidewire placement results by SpyGlass were recorded and analyzed.Results:Of the 24 patients, 9 were anastomostic strictures (AS) and 15 others were non-anastomostic strictures (NAS). The main characteristic of 5 initial AS patients was scar constriction. Whether treated or not, all of the 15 NAS patients showed evident inflammatory hyperplasia in hilar bile duct under SpyGlass, 80% (12/15) of which were accompanied with intrahepatic biliary stones. The strictures disappeared with mild hyperplasia in 8 patients (4 AS and 4 NAS) whose biliary stents were extracted. Eleven patients (5 AS and 6 NAS) needed guidwire placement under SpyGlass, six (54.5%) of whom succeeded. The successful rate in AS patients was higher than that of NAS (4/5 VS 2/6).Conclusion:The main characteristic of AS is scar constriction and that of NAS is inflammatory hyperplasia. Selective guidewire placement can be achieved by SpyGlass peroral choledochoscopy with a satisfactory successful rate in the difficult AS.