ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective:To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases.Methods:This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model.Results:Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cm×2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung ( n=36), kidney ( n=19), liver ( n=12), pancreas ( n=7), rectum ( n=3), stomach ( n=2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P>0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions:Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Objective:To observe any therapeutic effect of combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints in treating stroke-associated pneumonia (SAP).Methods:Eighty SAP patients were randomly divided into a treatment group and a control group, each of 40. Both groups were given routine symptomatic treatment for pneumonia, nutritional support, lipid-lowering and anti-infection measures, as well as acupuncture at the back-shu and front-mu acupoints. The treatment group additionally received pulmonary rehabilitation training. Before and after 14 days of the treatment, both groups were evaluated in terms of their forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak flow rate (PEF), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Chinese medicine (TCM) scores for expectoration of phlegm, shortness of breath, pulmonary rales, cough, fever and weakness were also assigned. The duration of antibiotic use and intensive care unit (ICU) stay were compared between the two groups.Results:Treatment efficacy was significantly higher in the treatment group (97.5%) than in the control group (85.0%). The treatment group′s average duration of antibiotic use and ICU stay were significantly shorter than in the control group. The treatment improved the average FVC, FEV1, PEF, WBC, CRP and PCT of both groups significantly leaving the average FVC and PEF of the treatment group significantly higher than the control group′s average, but its average WBC, CRP, PCT and the total TCM syndrome score significantly lower.Conclusions:Combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints has a definite therapeutic effect on SAP patients. It can significantly shorten the use of antibiotics and ICU stay, promote the recovery of lung function, reduce inflammation and relieve clinical symptoms.

Objective To verify the feasibility and maneuverability of fast bare-handed vertical slicing method for dry Chinese herbal medicine, and to provide reference of this method for different types of medicinal materials. Methods Several representative medicinal herbs were randomly selected in the market to make micro-slices using the top-slicing method to observe its cutting effect. Results Experiments showed that microscopic slices can be obtained for most herbs in a few minutes, which can be used for identification and quality testing. Conclusion This method is fast, effective, simple and practical. It meets the requirements of pharmacopoeia for microscopic identification. This method deserves for promotion.

OBJECTIVE: To explore the genetic etiology of a patient with glycogen accumulation type Ⅰa with gout as the main clinical feature. METHODS: Clinical data of the patient was collected. The patient and her parents were subjected to next generation sequencing (NGS). Suspected pathogenic variation was verified by Sanger sequencing. RESULTS: The patient, a 30-year-old women, mainly manifested hyperuricemia, chronic gouty arthritis, fasting hypoglycemia, hypertriglyceridemia, hyperlactatemia, hepatomegaly, urolithiasis, and gradually developed liver nodules and renal dysfunction. NGS revealed that she has carried c.648G>T (exon 5) and c.260delG (exon 2) compound heterozygous variants of the G6PC gene, which were respectively inherited from her father (phenotypically normal) and mother (with hyperuricemia). The c.260delG variant was unreported previously. Bioinformatic analysis indicated that both variants are pathogenic. CONCLUSION The compound heterozygous variants of the G6PC gene probably underlay the glycogen storage disease Ⅰa in this patient. G6PC gene mutations should be excluded in young women with hyperuricemia and /or gout.

Impaired eady phase insulin secretion is an important reason for leading to postprandial hyperglycemia.Nateglinide is a rapid-acting insulin secretagogue,which reduces postprandial blood glucose of type 2diabetic patient by restoring early phase insulin secretion.The efficacy and safety have been fully verified by clinical administration and it is more widely used to treat type 2 diabetic patients.Both sulfonylureas and glinides were named insulin secretagogue agents and regarded as alternative first-line drugs in the 2010 Chinese Guideline for treatment of type 2 diabetes.AACE/ACE Consensus statement claimed that glinides would be one of the important choices after metformin.In order to further guide the clinical application of nateglinide,16 national specialists in the field of endocrinology and metabolism of China discussed,drafted,and edited this consensus.The current consensus combined clinical evidences at home and abroad.systematically reviewed and summarized tlle results of these studies about nateglinide.It will provide guiding recommendations and reference concerning how to reasonably and effectively use nateglinide in the clinical practice.

In the teaching reform of genetics,we took the exploration of teaching reform mode in association with constructivism theory."One-center,both-balance,four-strategy combined"and combination of popularized education with elite education were the traits.The effects were favorable through the reform carried out both in theory teaching and experimental teaching.