Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Its occurrence secondary to hepatobiliary malignancies is even rarer, and without timely diagnosis and treatment, the mortality rate is extremely high. There is a need to raise awareness of this disease. This report describes a case of a 70-year-old female patient diagnosed with AHA 2 months after surgery for cholangiocarcinoma, admitted to the Second Affiliated Hospital of Bengbu Medical College in October 2022. The patient presented with subcutaneous hematoma in both lower limbs. Coagulation function tests showed a markedly prolonged activated partial thromboplastin time (APTT) of 74.5 seconds, with no correction in the APTT mixing test. Coagulation factor assays revealed a severely reduced coagulation factor VIII activity (FVIII:C) of 0.3%, and an inhibitor titer of 25.6 BU/mL was detected. After ruling out other potential causes, the patient was diagnosed with cholangiocarcinoma-associated AHA. With chemotherapy to control the primary tumor, alongside hemostatic and immunosuppressive therapy for inhibitor eradication, AHA was brought under control. The patient had no further coagulation abnormalities or bleeding, enabling timely and full-course chemotherapy for cholangiocarcinoma and significantly improving survival and quality of life. Therefore, in patients with malignancies who present with spontaneous bleeding or unusual bleeding following surgery, trauma, or invasive procedures, clinicians should be alert to the possibility of secondary AHA. Timely diagnosis and treatment can significantly improve prognosis.
Humans ; Cholangiocarcinoma/surgery* ; Female ; Hemophilia A/drug therapy* ; Aged ; Bile Duct Neoplasms/surgery* ; Factor VIII

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective To identify early Klebsiella pneumoniae(KP)infection after liver transplantation and its impact on prognosis.Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed,and they were divided into the non-infection(n=52)and infection groups(n=119)according to the bacterial culture results at postoperative 2 weeks.In the infection group,KP was not detected in 86 cases(non-KP infection group),and KP was cultured in 33 cases(KP infection group).Preoperative,intraoperative and postoperative data were statistically compared between the non-infection and infection groups,and between the non-KP infection and KP infection groups.The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed.Results Compared with the non-infection group,model for end-stage liver disease(MELD)score and total bilirubin level were higher,the operation time was longer,the length of postoperative intensive care unit(ICU)stay and the length of hospital stay were longer,the amount of intraoperative red blood cell transfusion was higher,the hospitalization expense was higher,the incidence of severe complications was higher,white blood cell count,absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher,absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group.The differences were statistically significant(all P＜0.05).Compared with the non-KP infection group,MELD score,total bilirubin level and aspartate aminotransferase(AST)level were higher,the operation time and the length of postoperative ICU stay were longer,the hospitalization expense was higher,the 90-d fatality was higher,the albumin level at postoperative 14 d was lower,and total bilirubin level at postoperative 30 d was higher in the KP infection group.The differences were statistically significant(all P＜0.05).Among 33 recipients with KP infection,16 cases were resistant to carbapenem antibiotics,and 7 of them died within postoperative 90 d.Seventeen cases were intermediate or sensitive to carbapenem antibiotics,and 4 of them died within postoperative 90 d.Preoperative MELD score ≥17 and operation time≥415 min were the independent risk factors for KP infection after liver transplantation(both P＜0.05).The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation(both P＜0.05).Conclusions KP infection is an independent risk factor for death after liver transplantation.High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation.

Objective:To investigate the application value of transanal intersphincteric resec-tion under direct vision in the Jackknife position in the anal preserving surgery for ultra-low rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 patients with ultra-low rectal cancer who underwent transanal intersphincteric resection under direct vision in the Jackknife position, combined with laparoscopic total mesorectal excision in Huizhou Municipal Central Hospital from September 2021 to November 2022 were collected. There were 9 males and 6 females, aged (63±9)years. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical and postoperative outcomes. All the 15 patients underwent operations successfully, without conversion to open abdo-minal operation. There were 5 cases of partial ISR and 10 cases of subtotal ISR. The operation time and volume of intraoperative blood loss of 15 patients were (260±30)minutes and 20(range, 10-30)mL, respectively. The distance from anastomosis to anal margin was (1.6±0.8)cm. The duration of post-operative hospital stay was 10(range, 8-13)days, and all 15 patients underwent colonic and anasto-mosis with staplers and protective ileostomy at the terminal ileum. Three patients had postoperative complications within 30 days after surgery, of whom 1 case with grade A anastomotic leakage was cured after conservative treatment and 2 cases with anastomotic membranous stenosis were cured by anal enlargement. (2) Postoperative pathological examination. The number of lymph nodes dissected of 15 patients was 18 ±6, and the distance between the tumor and distal resection margin was 1.3(range, 1.0-2.0)cm. The surgical specimens of all 15 patients showed complete mesorectum and negative for proximal, distal and circumferential margins. Results of postoperative pathological examination showed that there was 1 case in stage pT1N0M0, 9 cases in stage pT2N0M0, 1 case in stage pT2N1M0, 1 case in stage ypT0N0M0, 2 cases in stage ypT2N0M0, 1 case in ypT3N1M0 stage. The histological subtype showed 11 cases of moderately differentiated adenocarcinoma and 4 cases of well-differentiated adenocarcinoma. (3) Follow-up. All 15 patients were followed up for 15(range, 12-24)months. No local recurrence and distant metastasis of the tumor was found, and no tumor-related death occurred. All 15 patients underwent stoma closure. The postoperative anal function assessment of 15 patients showed no disorder in 5 cases, mild disorder in 8 cases and severe disorder in 2 cases.Conclusion:Transanal intersphincteric resection under direct vision in the Jackknife position in the anal preserving surgery for ultra-low rectal cancer is safe and feasible.

Objective To summarize clinical experience of transabdominal pericardial anastomosis of suprahepatic vena cava of the donor and right atrium of the recipient in liver transplantation for Budd-Chiari syndrome (BCS) complicated with liver cancer. Methods Clinical data of a BCS patient complicated with liver cancer undergoing transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation were retrospectively analyzed. Results The hepatic vein and suprahepatic vena cava were partially occluded in the patient. Liver transplantation was completed by transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium with beating-heart. In addition, due to pathological changes of the recipient's hepatic artery, splenic artery of the recipient was cut off, distal ligation was performed, and the proximal end was reversed and anastomosed with the common hepatic artery of the donor liver, and the reconstruction of hepatic artery was completed. The surgery was successfully performed. At approximately postoperative 1 week, the function of the liver allograft was gradually restored to normal, and no major complications occurred. The patient was discharged at postoperative 25 d. No signs of BCS recurrence was reported after 8-month follow-up. Conclusions It is safe and feasible to treat BCS by liver transplantation with transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium. BCS patients complicated with liver cancer obtain favorable prognosis.

Traditional pig breeding has a long cycle and high cost, and there is an urgent need to use new technologies to revitalize the pig breeding industry. The recently emerged CRISPR/Cas9 genome editing technique shows great potential in pig genetic improvement, and has since become a research hotspot. Base editor is a new base editing technology developed based on the CRISPR/Cas9 system, which can achieve targeted mutation of a single base. CRISPR/Cas9 technology is easy to operate and simple to design, but it can lead to DNA double strand breaks, unstable gene structures, and random insertion and deletion of genes, which greatly restricts the application of this technique. Different from CRISPR/Cas9 technique, the single base editing technique does not produce double strand breaks. Therefore, it has higher accuracy and safety for genome editing, and is expected to advance the pig genetic breeding applications. This review summarized the working principle and shortcomings of CRISPR/Cas9 technique, the development and advantages of single base editing, the principles and application characteristics of different base editors and their applications in pig genetic improvement, with the aim to facilitate genome editing-assisted genetic breeding of pig.
Animals ; Swine/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Breaks, Double-Stranded

Objective:To investigate the value of bone marrow plasma cell morphology in the diagnosis and prognosis of plasma cell myeloma (PCM).Method:Observational study.Collect the bone marrow morphology image reports and corresponding monoclonal protein (M protein) identification results of 1071 patients [629 males and 442 females, Median age 62 (29, 93) years] diagnosed with PCM in the outpatient and inpatient departments of Beijing Chaoyang Hospital affiliated to Capital Medical University from January 1, 2017 to February 28, 2022. Combined with Durie‐Salmon(DS) and International Staging System (ISS) of 427 patients diagnosed with PCM and overall survival time (OS) of 436, summarize the relevant plasma cell morphological characteristics. Statistical methods include chi-square test, Kruskal-Walls test, Spearman correlation analysis and Kaplan-Meier survival analysis.Result:The bone marrow morphology reports showed that the typical morphological features of peripheral blood in 573 patients with PCM included plasma cells (40.84%), immature granulocytes (30.89%), rouleaux formation in erythrocytes (68.94%) and nucleated red blood cells (8.55%). The types of bone marrow plasma cells in 1 071 patients diagnosed with PCM included 372 (34.73%) plasmablasts, 674 (62.93%)immature plasma cells, and 25 (2.34%) mature plasma cells. There is a significant positive correlation between the number of bone marrow plasma cells (proportion of nuclear cells) and the concentration of IgG and IgA type, from M protein identification( r=0.55, r=0.60, P<0.01). The proportions of M protein types in 1 071 patients with PCM from high to low were IgG (45.75%), IgA (23.53%), light chain (19.61%), IgD (4.76%), non-secretory (4.3%), biclonal (1.78%), IgE (0.19%), IgM (0.08%). The typical characteristics of the bone marrow plasma cells in various M protein types included clustered distribution, different cell body sizes, inclusions in the cytoplasm, binuclear, polynuclear, and abnormal nuclear. The proportion of plasmablasts in DSⅢ stage was 44.81% (164/366), higher than 21.57% (11/51) in DSⅡstage, and the difference was statistically significant(χ 2=10.2, P<0.05). There was a significant positive correlation between the number of bone marrow plasma cells and DS and ISS stages( r=0. 0.23, r=0.30, P<0.01). The median OS of the PCM patients in the plasmablasts group was significantly shorter than that in the immature plasma cells group [56.0 (23.0, 101.8) months vs 75.9(31.6, 121.5) months, HR=1.42,95% CI 1.05-1.91, P=0.02]. The median OS of the PCM patients in the group of tumor plasma cells burden≥37.5% was shorter than that of the tumor plasma cells burden<37.5% [75.9 (21.4, 122.6)months vs 81.3 (36.6, 108) months, HR=1.54,95% CI 1.14-2.07, P<0.05]. Conclusion:The morphology and tumor burden of bone marrow plasma cells provide an important basis for the diagnosis of PCM and can be used as a prognostic indicator for patients with PCM.

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

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 explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.