OBJECTIVE: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement.
METHODS: We conducted a retrospective analysis of all adults with LCH (≥ 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022.
RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%).
RESULTS: After a median 40 months\' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, P = .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, P = .010) correlated with superior PFS versus chemotherapy.
CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.

Under the background of food security, using non-grain feed instead of corn-soybean-based feed is an effective measure to alleviate the food-feed competition. While, non-grain feeds are often rich in fiber, which cannot be digested by non-ruminants. Producing heterologous enzymes in non-ruminants to improve cellulose utilization rate is a new research strategy by transgenic technology. In this study, porcine transthyretin (TTR) promoter, signal peptide-coding sequence (CDS), Saccharomycopsis fibuligera β-glucosidase gene (BGL1)-CDS, 6×His sequences fragments were fused into pGL3-control vector to generate transgenic vector. Then, transgenic mice were generated by pronuclear microinjection of the linearized expression vectors. Transgenic mice and their offspring were examined by PCR-based genotyping and copy number variation. Results showed that BGL1 was successfully integrated into the mouse genome and transmitted stably. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and β-glucosidase activity assay demonstrated that BGL1 was specifically expressed in the liver, and β-glucosidase activity significantly increased. In addition, liver weight index, cellular morphology, and collagen fiber content of the liver showed that exogenous gene insertion did not cause any lesions to live. Taken together, our findings suggest that β-glucosidase driven by TTR promoter was specifically expressed in the liver of transgenic mice.

Obstructive azoospermia (OA) is an important cause of male infertility, and epididymal OA (EOA) is a common disease. Microsurgical reconstruction is a common technique used in the treatment of EOA. In the present study, we analyzed the effectiveness of microsurgical vasoepididymostomy (MVE) at different levels and compared the differences among several MVE techniques.
A literature search was conducted in the PubMed, Web of Science, and Embase databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included studies were published in English until May 14, 2021. The R 4.1.2 software was utilized to evaluate the event rate, risk ratio (RR), and 95% confidence interval (CI).
A total of 51 studies involving 2853 patients with OA were included in our meta-analysis. The overall mean patency rate of patients who underwent MVE was 67.20% (95% [CI]:63.30%-71.10%), and the overall mean natural pregnancy rate of their partners was 40.05% (95% [CI]: 35.30%-45.60%). The pooled results showed that the patency rate of bilateral MVE was higher than that of unilateral MVE (RR = 1.42; 95% [CI]:1.25-1.61; p < 0.00). A comparison of the anastomotic site of MVE showed that the caudal/corpus area was favorable for the patency rate (RR = 1.17; 95% [CI]:1.04 - 1.32; p < 0.00). The caudal area was also advantageous for the patency rate (RR = 1.20; 95% CI:1.03 - 1.41; p < 0.04). Compared with typical MVE (65.20%, 95% [CI]:61.40%-69.10%), deferential vessel-sparing MVE with a higher overall mean patency rate (83.60%, 95% [CI]:75.40%-91.70%).
The meta-analyses indicated that MVE is a high- and cost-effective therapeutic method for patients with EOA, and deferential vessel-sparing MVE could be mainstream in the near future.

There are many glucose-lowering agents used in patients with heart failure, showing mixed results, this study was conducted to determine the effect of liraglutide, a glucagon-like peptide-1 analogue, on the treatment of patients with heart failure. Patients from the FIGHT and LIVE trials were included, all overlapped data were summarized and described. No significant changes from baseline in left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, hemoglobin A1c, heart rate, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, and 6 min walk test were observed in FIGHT. In LIVE, liraglutide significantly decreased hemoglobin A1c and inceased 6 min walk test and increased heart rate and serious cardiac adverse events, and there were no statistical differences in left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, left ventricular end-systolic volume index, and left ventricular end-diastolic volume index. In this study, we found that there is not enough reason to support the use of liraglutide in patients with heart failure, and importantly, the safety of liraglutide in this particular population remains uncertain. Enhanced recognition the risks and benefits of liraglutide would help guide therapeutic decisions in patients with heart failure.

Various training models have been developed for laparoscopic training. Inanimate models including cadavers, ex-vivo simulator, and virtual reality (VR), are less realistic and often fail to display specific events such as bleeding, bile leakage, etc. Animal models provide more realistic experience, but constraints like cost involved, anesthetic requirement, and ethical approval have limited its application. We have designed a new training ex-vivo simulator-Smagister to address these issues.
The Smagister consists of a normothermic machine perfusion platform, multivisceral organ of porcine abdominal cavity (liver, gallbladder, pancreas, stomach, intestine, kidney, uterus, bladders, etc.), high-definition display, and software system. Blood gas analysis and number of peristalsis per hour were recorded. A questionnaire was used to subjectively assess vitality of the organ cluster every hour. Three laparoscopic procedures including cholecystectomy (LC), enterotomy closure (LEC) and hepatectomy (LLR) were performed on Smagister, with demonstration of specific events for each procedure. Six experts compared the procedures with actual surgery in terms of feasibility to complete procedures and demonstration of complications.
The fluctuation of perfusate glucose (6.1-8.2 mmol/L) and lactate (5.82-6.55 mmol/L) suggested metabolic function of the multivisceral organs. The mean number of peristalsis was 2.2/min. The simulated surgical view and anatomic structures closely resembled actual surgery during continuous perfusion (3.5 ± 1.0, 3.8 ± 0.8, respectively). The evaluation scores of haptic feedbacks were 3.8 ± 0.8, resembling live tissue handling. LC, LEC, and LLR were performed well on the Smagister, with clear display of the specific events. All six experts considered Smagister as a suitable training modality for both basic and advanced laparoscopic surgery.
The amalgamation of live animal model and ex-vivo simulation in Smagister centralizes the virtue of both modalities, expands the training field, and provides high-fidelity laparoscopic training for both novice and senior surgeons.

OBJECTIVE: To evaluate outcomes relative to treatment using systemic methotrexate (MTX) alone or systemic MTX combined with ultrasound (US)-guided local injection of potassium chloride (KCl) or MTX in women with live tubal ectopic pregnancies.
METHODS: Case-control study (Canadian Task Force classification II-2).
METHODS: Departments of Obstetrics and Gynecology in 2 hospitals in China.
METHODS: Eighty-two women with live tubal ectopic pregnancies.
METHODS: Participants in the study received treatment using either systemic MTX (n = 37; systemic treatment group) or systemic MTX and US-guided local injection of either MTX or KCl (n = 45; combined treatment group).
RESULTS: Patient clinical features and outcomes were compared. There were no significant differences between the patient groups insofar as baseline gestational age, β-human chorionic gonadotropin concentration, or size of conceptus. The success rate in patients who received combined therapy (93.3%) was much higher than in those who received only systemic treatment (73.0%) (p < .05). In the combined treatment group, the success rate was similar between women who received locally injected KCl (95.2%) and those who received locally injected MTX (91.7%).
CONCLUSIONS: The significantly higher success rate in patients who received combined US-guided local injection and systemic MTX suggests that this is an efficient nonsurgical option in women with tubal pregnancy, high serum β-human chorionic gonadotropin concentration, and fetal cardiac activity.