Primary liver cancer ( PLC) , the most com-mon malignant carcinoma in the world , greatly impairs the hu-man health .Various treatments for PLC have been practiced but the therapeutic effects are still unsatisfied .Nowadays, interven-tional therapy , chemotherapy , radiotherapy , molecular targeted therapy and radiofrequency ablation are playing a key role in hepatocellular carcinoma treatment .In near future , more ad-vancements on comprehensive therapy for PLC are being expec-ted.This review aimed to describe the recent scenario and cur-rent advancement on non-surgical treatment for hepatocellular carcinoma .

Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

OBJECTIVES: Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury. METHODS: Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)]. RESULTS: There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05). CONCLUSIONS Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.
AMP-Activated Protein Kinases/metabolism* ; Acute Kidney Injury/pathology* ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/pharmacology* ; Autophagy ; Caspase 3/metabolism* ; Caspase 9/metabolism* ; Female ; Humans ; Ischemia ; Kidney/pathology* ; Leptin/pharmacology* ; Male ; Mammals/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Reperfusion/adverse effects* ; Reperfusion Injury/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Objective:To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up.Methods:Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups.Results:Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio ( HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO ( P<0.05). Conclusion:Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases.

【Objective】 To compare the diagnostic value of endoscopic ultrasonography (EUS) with conventional imaging in pancreatic occupying lesions so as to provide guidance for the diagnosis of pancreatic occupying lesions. 【Methods】 We selected patients who underwent EUS in the Digestive Endoscopy Room of The First Affiliated Hospital of Xi’an Jiaotong University from September 2012 to December 2019 and were strictly screened by ultrasound endoscopists and diagnosed as pancreatic space-occupying lesions as the study subjects, and collected routine imaging examination results and related information and data of the patients (age, gender, tumor markers, blood amylase, urine amylase, and serum lipase) at the same time. We compared the sensitivity, specificity and accuracy of EUS and conventional imaging methods in the diagnosis of pancreatic space-occupying lesions, and evaluated their diagnostic value. 【Results】 A total of 188 cases were included, with more male ones than female ones. The age of patients in the tumor group was higher than that in the non-tumor group, and the levels of tumor markers serum CA-199 and CEA were significantly higher than those in the non-tumor group. The diagnostic sensitivity of pancreatic space-occupying lesions supported EUS (95.5%), which was significantly better than that of transabdominal ultrasound (54.4%), plain CT (57.1%), enhanced CT (75%), MRI (66.7%), PET-CT (72.7%) and other conventional imaging examination methods. The diagnostic accuracy of pancreatic space-occupying lesions supported EUS (91.5%), better than transabdominal ultrasound (58.3%), plain CT (57.1%), enhanced CT (74.6%), MRI (62.5%), and PET-CT (66.7%). The negative predictive value of the diagnosis of pancreatic space-occupying lesions supported EUS (76.7%), better than transabdominal ultrasound (27.9%), plain CT (22.9%), and enhanced CT (38.1%). 【Conclusion】 In the diagnosis of pancreatic space-occupying lesions, EUS is significantly better than conventional imaging methods such as transabdominal ultrasound, plain CT, enhanced CT, MRI, and PET-CT, and the negative predictive value of EUS is significantly better than that of transabdominal ultrasound, plain CT and enhanced CT.