Chronic heart failure is the terminal stage of various cardiovascular diseases， and cardiomyocyte apoptosis is the turning point of decompensation. Studies have shown that traditional Chinese medicine （TCM） could regulate apoptosis-related signaling pathways and factors and inhibit or up-regulate the expression of apoptosis-related proteins. Thus， TCM can reduce cardiomyocyte apoptosis， protect the myocardial tissue and improve the cardiac function， demonstrating remarkable clinical effects. In recent years， the research on the treatment of chronic heart failure based on the inhibition of cardiomyocyte apoptosis is increasing and becomes the current research hotspot. On the basis of literature review， this paper discovers that TCM regulates apoptosis factors and multiple signaling pathways to inhibit apoptosis and inflammation and delay the progression of chronic heart failure through classical pathways such as the death receptor pathway， the mitochondrial pathway， and the endoplasmic reticulum pathway. At the same time， the studies in this field have the following problems： Repeated studies with shallow， simple， and fragmented contents， treating animal models with TCM prescriptions without syndrome differentiation， treating diseases with drugs at only one concentration which is insufficient to indicate efficacy， and lacking comprehensive， holistic， and systematic studies on the relationships of apoptosis with inflammatory responses， pyroptosis， ferroptosis， and autophagy. In the future， more scientific， reasonable， comprehensive， and feasible experimental schemes should be designed on the basis of comprehensively mastering the research progress in this field， and the communication and cooperation between researchers in different disciplines should be strengthened. The specific pathological mechanism of cardiomyocyte apoptosis in chronic heart failure and the signaling pathways， active components， and action targets of TCM in inhibiting cardiomyocyte apoptosis in chronic heart failure should be elucidated. Such efforts are expected to provide sufficient reference for the clinical treatment of chronic heart failure.

Objective To compare the safety and efficacy of flexible terminal suction ureteral access sheath(FTS-UAS)and negative pressure ureteral access sheath(NPUAS)in flexible ureteroscopic lithotripsy with holmium laser in treatment of renal calculi less than 2 cm in diameter.Methods A total of 68 patients(largest diameter of stone＜2 cm)with renal calculi treated in Yangjiang Hospital Affiliated to Guangdong Medical University during Nov.2022 and Aug.2023 were divided into FTS-UAS group(n=34)and NPUAS group(n=34)according to different surgical methods.The perioperative parameters and stone-free rate(SFR)were compared between the two groups.Results The average SFR on the first day after operation was significantly higher in the FTS-UAS group than in the NPUAS group[85.3％(29/34)vs.61.8％(21/34),P=0.028].The operation time was significantly lower in the FTS-UAS group than in the NPUAS group[(65.85±13.16)min vs.(75.59±20.21)min,P=0.022].For lower calyceal renal calculi,the SFR was significantly higher in the FTS-UAS group than in the NPUAS group[82.4％(14/17)vs.43.8％(7/16),P=0.032].One month after operation,the SFR was higher in the FTS-UAS group than in the NPUAS group[94.1％(32/34)vs.85.3％(29/34),P=0.452].There were no significant differences in hemoglobin reduction,serum creatinine level,postoperative complications,hospital stay and hospitalization costs between the two groups(P＞0.05).Conclusion FTS-UAS in flexible ureteroscopic lithotripsy can shorten the operation time and improve stone-clearance rate,which is safe,effective,and worthy of clinical promotion.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective To compare the prognosis of cognitive dysfunction in patients with cerebral hemorrhage and cerebral infarction by observing the effect of comprehensive rehabilitation intervention based on attention and working memory on the patients with cognitive dysfunction after cerebral hemorrhage and cerebral infarction.Methods A total of 44 patients with cognitive dysfunction after stroke admitted to the Rehabilitation Department of the First Hospital of Jilin University from September 2018 to January 2021 were selected，including 19 patients with cerebral infarction and 25 patients with cerebral hemorrhage，aged from 18 to 80 years，with the course of disease ranging from 2 weeks to 12 months. Both groups received cognitive training based on attention and working memory and conventional rehabilitation therapy，cognitive training 20 minutes a day,6 days/ week，for 4 weeks. Routine rehabilitation includes physical factor therapy，exercise therapy，occupational therapy，aerobic exercise，acupuncture，etc. Montreal Cognitive Assessment（MoCA） was used to assess Cognitive function in all patients before and after treatment.Results After treatment，MoCA scores of 2 groups were significantly higher than those before treatment，the difference was statistically significant（P<0.05）；The improvement of MoCA scores in cerebral hemorrhage group was higher than that in cerebral infarction group，and the difference was statistically significant（P<0.05）.Conclusion Comprehensive rehabilitation intervention based on attention and working memory can effectively improve the level of cognitive function in patients with intracerebral hemorrhage and cerebral infarction，and the prognosis of cognitive function after intracerebral hemorrhage may be better.

OBJECTIVETo investigate the outcomes, survival status, and the prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patients.

METHODSA retrospective study was carried out to analyze the clinical data of 61 EBV-HLH cases, from January 2008 to July 2014. Prognostic factors were analyzed through COX model (single factor and multiple factors).

RESULTSA total of 246 patients with HLH were diagnosed, among which 102 cases were with EBV infection (including 61 EBV-HLH, 36 lymphoma associated HLH, 5 primary HLH. Among the 61 cases, 40 were male and 21 were female, with a ration of 1.9:1. The median age was 28 years (range, 12-78). 1, 3, 6 and 12-month overall survival rates of 61 EBV-HLH were 65.6%, 47.5%, 32.4%, and 25.0%, respectively. The median follow-up time was 3 (0.5-28) months. 12 patients didn't use etoposide within 4 weeks after diagnosis, while HLH-94 protocol was used in 33 patients and HLH-2004 protocol was used in 16 patients. Response rates of theses three groups were 33.3%, 51.5%, and 43.8%, respectively (P=0.401). There was statistically difference between the group without etoposide and the HLH-94/ HLH-2004 group in the overall survival rate (P=0.033). Serum albumin level (P=0.033) and whether EBV could became negative (P=0.010) were independent predictors for EBV-HLH.

CONCLUSIONEBV-HLH patients have severe clinical feature and poor prognosis. Early application of immune chemotherapy based on etoposide can improve survival. Serum albumin level and whether EBV can become negative are independent prognostic factors for survival.

Adolescent ; Adult ; Aged ; Child ; Epstein-Barr Virus Infections ; Etoposide ; Female ; Herpesvirus 4, Human ; Humans ; Lymphohistiocytosis, Hemophagocytic ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH).

METHODSA retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013.

RESULTSOf the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P<0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance.

CONCLUSIONThe secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis.

Adult ; Bone Marrow ; Fever ; Humans ; Killer Cells, Natural ; Lymphohistiocytosis, Hemophagocytic ; Prognosis ; Retrospective Studies

Objective To evaluate the clinical efficacy of factional multiplex laser (AffirmTM) with combined apex pulse (CAP) technology in treating depressive acne scars,post inflammatory erythema and enlarged pores and other lesions.By following up,the correlative factors were analyzed to guide the further use of the factional laser (AffirmTM) with CAP technology.Methods Patients who received the AffirmTM laser therapy from Sept.2007 to July 2008 were enrolled in this retrospective follow-up study.Pictures were taken before and after each treatment during the therapy.Then the pictures were evaluated by dermatologists to attain object variables.Other subject variables from patients were recorded during survey.The relation between the efficacy and age,sex and treatment frequencies were analyzed statistically.Results The effective rate was 25.34 ％ for post-acne scars,36.84 ％ for post-acne erythema.28.57 ％ for enlarged pores,and 14.29 ％ for rythids.Nonparametric test showed no statistical difference with gender or age.There was correlation between efficacy and treatment frequencies.No severe adverse effect was observed.Conclusions AffirmTM laser with CAP technology has a good effect on treating post-acne depressed scars and erythema,enlarged pores and fine rythids.

Objective To evaluate the safety and efficacy of polymethylmethacrylate/PMMA (Artecoll) as an injectable dermal filler after using laser, radiofrequency and intensive pulse light. Methods In vitro, factional photothermolysis (Affirm) was directly used on the PMMA to see if there was any change in the structure or surface smoothness. In vivo, pig and guinea pig were used as the short-term and long-term models, respectively, for Artecoll. The dermal filler was first injected and then laser treatments conducted.The skin sample was observed through light microscope, scanning electronic microscope and transmission electronic microscope to see whether there were any structural changes, infiltration of inflammatory cells and the regeneration of collagen. Results Through the microscopic observation of in vitro experiment and the animal models, no distortion or rupture of the microsphere were found after the laser treatment. No uneven surface was found in the PMMA microsphere either. The microshpere was surrounded by the inflammatory cells. The infiltration was mild to intermediate with few foreign body giant cells even after several treatments of laser. There was no macrophage seen. But the collagen regeneration was distinguishable after the laser treatment. No obvious structural change was found eventually. Conclusion Artecoll is a safe and effective permanent injectable dermal filler for wrinkle reduction and contour refining.

OBJECTIVETo investigate the association of the 1891-1892del TC polymorphism of regulator of G-protein signalling 2 (RGS2) gene with hypertension in Xinjiang Kazakh population.

METHODSThe case-control study was performed in 444 cases and 489 controls. The genotypes of the individuals in the 1891-1892del TC locus were identified by TaqMan method.

RESULTSA significant association was observed between the1891-1892TC insertion/deletion polymorphism with hypertension in men (OR=1.698, P=0.03) and in the total population (OR=1.32, P=0.044). The mean systolic blood pressure and serum uric acid levels of the ID+DD carriers were significantly higher than that of the II carriers (adjusted, P=0.04 and P<0.01).

CONCLUSIONThe results suggest that the D allele of the 1891-1892TC insertion/deletion locus of the RGS2 gene might be an independent risk factor for hypertension in Xinjiang Kazakhs; and the polymorphism may have some influence on serum uric acid level in this population.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Pressure ; Case-Control Studies ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Hypertension ; blood ; ethnology ; genetics ; physiopathology ; Male ; Middle Aged ; Polymorphism, Genetic ; RGS Proteins ; genetics ; Risk Factors ; Uric Acid ; blood

Objective Atherosclerosis is widely accepted as a chronic inflammatory disease. Serum biomarkers for vulnerable plaques not only serve as diagnostic tools for the identification of patients with acute coro-nary syndrome, but also assist the identification of high-risk patients. However, the existing data are limited and conflicting. In the present study, we determined whether the plasma levels of interleukin-1β (IL-1β) are correlated with adverse cardiac outcomes in patients with ST-evaluate acute myocardial infarction (STEAMI) undergoing pri-mary percutaneous coronary intervention (PCI). Effect of the plasma intedeukin-1β level on prognosis of patients with ST-segment elevation acute myocardial infarction. Method This prospective single-center study included 96 patients with SIEAMI with onset < 12 h who underwent primary PCI, 271 patients with stable angina pectoris (SAP) and 148 control subjects without coronary artery disease who were consecutively admitted to hospital be-tween Mar, 2006 and Mar, 2008. Plasma IL-1β levels were measured by enzyme-linked immunosorbent assay in all subjects. The patients with STEAMI were then followed prospectively for the occurrence of major adverse car-diac events (MACE) (including cardiovascular death, non-fatal myocardial infarction, heart failure, and cardio-genie shock) during hospitalization. We determined the association between IL-1β levels with the risk of MACE using multivariate logistic regression. Results Compared with the SAP patients and control subjects, patients with STEAMI had higher levels of IL-1β (P < 0.05). During hospitalization, 32 patients (33.3%) experienced MACE [23 males, 9 females; age: (75.44±13.45) years]. In the STEAMI patients, IL-1β was elevated in patients with MACE compared with patients without MACE (median [range]: 26.52 [12.010 to 155.244] pg/mL vs 2.157 [0.433 to 83.021] pg/mL; P < 0.01) by non-parameter analysis. Significant and positive correlations be-tween IL-1β and cardiac troponin-I (cTnI) (r = 0.353, P =0.004) were observed by Spearman's correlations analysis. Multivariate logistic regression analysis revealed that IL-1β levels ≥20 pg/mL were significantly and in-dependently associated with MACE during hospitalization (odds ratio: 32.05; 95% confidence interval: 4.28 to 240.151; P =0.001). Conclusions The present study revealed that patients with STEAMI had elevated IL-1β levels on admission. The plasma IL- 1β level is an independent inflammatory predictor for in-hospital MACE in pa-tients with STEAMI undergoing percutaneous coronary intervention.