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

BACKGROUND: Lung cancer rates among women in rural Xuanwei and Fuyuan counties in eastern Yunnan province, China, are among the highest in the world, even though almost all women are non-smokers, and they tend to develop lung cancer at a younger age than other locations by roughly 5 yr-10 yr. This study investigated the survival of lung cancer patients among female never-smokers. METHODS: The female never-smokers, who had lived for many years in Xuanwei and Fuyuan counties, with lung cancer newly-diagnosed between July 2006 to March 2010, were followed up through the end of 2016. Age-standardized relative survival for all cases was calculated using local life table. The Kaplan-Meier method and Log-rank test were used to analyze the relationship between the variables and the prognosis in univariate analysis. Cox regression analysis was employed in the multivariate analysis. RESULTS: Among 1,250 total subjects, 1,075 died and the remaining 175 were censored during the follow-up, with a median follow-up period of 69 months (95%CI: 61.9-76.0). Overall, the mean age was (54.8 ±10.9) yr, with variable clinical stages: 3.5% of cases were stage I, 8.7% stage II, 20.7% stage III, 29.7% stage IV, and 37.4% stage unknown. The 645 patients(51.6%) with cyto-histological diagnosis contains 303 with Squamous cell carcinoma, and 231 with adenocarcinoma, 24 with small cell, 43 with other specified type and 39 with unknown histological type. Only 215 (17.2%) patients received surgery, 487 (39.0%) were treated without surgery, and 548 (43.8%) did not receive any specific anticancer therapy. The 5-year observed survival rate and age-standardized relative survival were 8.9% (95%CI: 7.0-10.6), and 10.1% (95%CI: 3.7-20.5) respectively, with a median survival of 13.2 months. The 5-year survival rates were 41.1% for stage I, 22.4% for stage II, 5.3% for stage III, 1.3% for stage IV, 11.2% for missing stage, 17.9% for adenocarcinoma, and 5.6% for squamous cell carcinoma respectively. Surgery significantly improved 5-year survival rate compared with non-surgery (34.8% vs 3.2%, P<0.001). The patients with non-treatment, aged 65 years and older, living in rural areas and farmer with low socioeconomic status had poorer survival, whereas the patients treated in provincial hospitals and chest X-ray screening had better survival. Cox multivariate analysis further showed that stage of tumor-node-metastasis (TNM), treatment status, hospital-level, and X-ray screening were factors correlated with survival. CONCLUSIONS Patients with lung cancer among female never-smokers in Xuanwei and Fuyuan experience poorer survival, because they are less likely to be diagnosed at early stage, as well as less likely to receive surgery and comprehensive treatment. Furthermore low socioeconomic status and poor health security are also responsible for the low survival.

BACKGROUND AND PURPOSE: Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke. METHODS: The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed. RESULTS: During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; P(linear-trend)=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke (P(non-linear)=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; P(linear-trend)=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol. CONCLUSIONS: These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.
Calcium ; Cholesterol ; Cohort Studies ; Diabetes Mellitus ; Follow-Up Studies ; Hypertension ; Medical Records ; Methods ; Stroke

PURPOSE: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. MATERIALS AND METHODS: In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary end-point was progress-free survival (PFS). RESULTS: The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the high-SAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. CONCLUSION: The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.
C-Reactive Protein* ; DNA* ; Herpesvirus 4, Human* ; Humans ; Observational Study ; Prognosis ; Prospective Studies* ; Serum Amyloid A Protein* ; Survival Analysis

BACKGROUND: Few studies have examined the association between mercury exposure and obesity. The aim of this study is to investigate the association between blood mercury concentrations and indices of obesity in adults. METHODS: A total of 200 healthy subjects, aged 30 to 64 years, who had no history of cardiovascular or malignant disease, were examined. Anthropometric and various biochemical profiles were measured. Visceral adipose tissue (VAT) was measured using dual-energy X-ray absorptiometry (DXA). RESULTS: All subjects were divided into three groups according to blood mercury concentrations. Compared with the subjects in the lowest tertile of mercury, those in the highest tertile were more likely to be male; were current alcohol drinkers and smokers; had a higher body mass index (BMI), waist circumference (WC), and VAT; had higher levels of blood pressure, fasting glucose, and insulin resistance; and consumed more fish. The blood mercury concentration was significantly associated with anthropometric parameters, showing relationships with BMI, WC, and VAT. After adjusting for multiple risk factors, the odds ratios (ORs) for high mercury concentration was significantly higher in the highest VAT tertile than in the lowest VAT tertile (OR, 2.66; 95% confidence interval, 1.05 to 6.62; P<0.05). CONCLUSION: The blood mercury concentration was significantly associated with VAT in healthy adults. Further studies are warranted to confirm our findings.
Absorptiometry, Photon ; Adiposity* ; Adult* ; Blood Pressure ; Body Mass Index ; Fasting ; Glucose ; Healthy Volunteers ; Humans ; Insulin Resistance ; Intra-Abdominal Fat ; Male ; Obesity ; Odds Ratio ; Risk Factors ; Waist Circumference

Traditional Chinese medicine(TCM) pill, the most representative and successive dosage form, is called as one of the four classical TCM dosage forms. "Pills could keep the lasting and lenitive therapeutic efficacy for a long period" is the most classical dosage form theory, showing a guidance significance in making recipe, preparations and clinic application. In this article, we would elucidate the inheritance and development significance of TCM pills in three key points, including dosage form theory, pharmaceutical preparation technology and clinic usage based on the pharmaceutics connotation of this theory. From this, it can provide the basis for researches on pills mechanism, material basis and mode of action in clinical application.

The manufacturing process of Chinese medicines is the significant link to achieve "effect-enhancing and toxicity-reducing", including an interaction between "toxicity and effect". This paper would elucidate the effects of Chinese herbal compound decoction, preparation, dosage forms, route of administration and quality of pharmaceutical excipients on "toxicity-effect" theory from the formulation approaches. The article pointed out that the comprehensive analysis on "toxicity-effect" theory should be strengthened from the aspects of overall manufacturing, fundamental research and modern Chinese preparation, to explore the mechanism of "effect-enhancing and toxicity-reducing" in the manufacturing process, clarify the core status of Chinese preparation in "toxicity-effect" theory, and ensure the security and effectiveness in traditional Chinese medicine clinical application.

OBJECTIVETo establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.

METHODSOne hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.

RESULTSRats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.

CONCLUSIONAnticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Animals ; Anticoagulants ; pharmacology ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Heparin, Low-Molecular-Weight ; pharmacology ; Hypertension, Pulmonary ; drug therapy ; metabolism ; Lung ; pathology ; Morpholines ; pharmacology ; Pulmonary Embolism ; drug therapy ; metabolism ; Rats ; Rivaroxaban ; Thiophenes ; pharmacology ; Warfarin ; pharmacology

OBJECTIVE: To observed the prevention efficacy of secretory otitis media after radiation therapy by the Myrtol Standardized Enteric Coated Soft Capsules. METHOD: Sixty patients with nasopharyngeal carcinoma who Diagnosis without secretory otitis media before radiation therapy were divided into experimental group and control group, 30 cases in each group. After the start of radiation therapy ,the experimental group patients oral the Myrtol Standardized Enteric Coated Soft Capsules, each 0.3 g, 3 times a day, 7 days a course of treatment, oral the medication three months, the patients in the control group received no treatment. 3 months and 6 months after the end of radiation therapy, whether there is a difference comparison of experimental group and the control group in symptoms, signs, pure tone audiometry and tympanogram change. RESULT: Seventeen patients (18 ears) (56.67%, 17/30) in the control group were suffering from secretory otitis media, 7 patients (7 ears) (23.33%, 7/30) in the experimental group were suffering from secretory otitis media. The difference between the two groups was statistically significant (P < 0.01). 17 patients (17 ears) in the control group and 7 patients (7 ears) in the experimental group were suffering from tinnitus. 20 patients(20 ears) in the control group and 9 patients (10 ears) in the experimental group have ear choking feeling. The difference between the two groups was statistically significant (P < 0.01). The air conduction hearing threshold of the experimental group before radiation therapy is (7.5 +/- 2.0) dB HL and the air conduction hearing threshold of the control group patients is (8.3 +/- 4.0) dB HL. The difference between the two groups was not statistically significant (P > 0.05). 3 months after radiation therapy,the gas conductive hearing threshold of the experimental group is (25.6 +/- 3.0) dB HL, but the data in the control group is (40.7 +/- 5.0) dB HL. The difference between the two groups was statistically significant (P < 0.01). CONCLUSION Patients with nasopharyngeal carcinoma oral the the Myrtol Standardized Enteric Coated Soft Capsules before radiation therapy can effectively reduce the incidence of secretory otitis media after radiotherapy, it can prevent the occurrence of secretory otitis media.
Adult ; Aged ; Aged, 80 and over ; Carcinoma ; Drug Combinations ; Female ; Humans ; Male ; Middle Aged ; Monoterpenes ; therapeutic use ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; radiotherapy ; Otitis Media with Effusion ; etiology ; prevention & control ; Radiotherapy ; adverse effects

Objective To investigate the impact of nutritional risk of preoperative patients with different parts of colorectal cancer. Methods 385 cases of surgical patients diagnosed with colorectal cancer were selected in the retrospective study in April 2008 to March 2009, Gastrointestinal Surgery Center of West China Hospital in Sichuan University. Patients were divided into the right colon cancer group, the left colon cancer group, the rectal cancer group, using internationally recognized NRS- 2002 Scale and serum nutrition indicators to assess their preoperative nutrition. Results NRS-2002 score in the right colon cancer group showed higher than the left colon and rectal cancer group, but no statistical difference between the latter two rates; serum concentrations of HGB, TP, ALB, A/G were lower in the right colon cancer group than the other two groups, but the concentrations of ALT, AST, Ca2+, PO43-showed no statistical difference among three groups. Conclusions The proximal colon (right colon cancer) were more susceptible to the risk of preoperative malnutrition, the patients with different parts of colorectal cancer should be given to the corresponding preoperative nutritional assessment and nutritional support.