Objective:To study the relationship between rs 2228314 polymorphism in sterol regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid levels in children and adolescents . Methods:In our study , 2 030 children and adolescents aged from 7 to 18 years participated .Anthropo-metric measurements, including height and weight, were performed.Their serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol ( HDL-C) were detected .The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS ) was used to detect rs2228314 genotypes.Results: The GC/CC genotypes of rs2228314 polymorphisms had lower HDL-C levels than GG genotype [(0.10 ±0.35) mmol/L vs. (0.14 ±0.36) mmol/L, P=0.020].The rs2228314 polymorphism was associated with the abnormal HDL-C level under the dominant model after adjustment for study samples , sex and age ( OR=1.400, 95%CI:1.027-1.907, P=0.033).The rs2228314 polymorphism was not associated with obesity un-der the dominant model after adjustment for study samples , sex, age and HDL-C level ( OR=1.178, 95%CI: 0 .971 -1 .430 , P =0 .096 ) . Conclusion: The GC/CC genotype carriers of SREBP2 rs2228314 polymorphism have higher risk of abnormal HDL-C level than the individuals with GG geno-type among children and adolescents .

BACKGROUND:Studies have reported that taurine has a certain therapeutic effect on the disease of various systems, such as nervous system, cardiovascular system, immune system and digestive system. The liver is the main place, also the important target organ, of taurine metabolism. Therefore, the relationship between taurine and hepatopathy has become a hot topic in recent years. OBJECTIVE:To investigate the influence of taurine on superoxide dismutase and malondialdehyde expression in the liver tissue of rat models of liver fibrosis induced by carbon tetrachloride. METHODS:Thirty male C57B/L rats of SPF grade were randomly and evenly divided into blank control, model and taurine groups. Rats in the blank control group were intraperitonealy injected with 100% peanut oil of 1 mL/kg, twice a week, in total 10 weeks. Rats in the model group were intraperitonealy injected with peanut oil of 1 mL/kg containing 20% carbon tetrachloride, twice a week, in total 10 weeks. Rats in the taurine group were intraperitonealy injected with peanut oil of 1mL/kg containing 20% carbon tetrachloride, twice a week, in total 10 weeks, and were intragastricaly administered taurine of 500 mg/kg per day starting from the 3rd week til the 10th week. RESULTS AND CONCLUSION:Compared with the blank control group, the serum levels of hyaluronic acid, laminin, typeⅢ procolagen, typeⅣ colagen, alanine aminotransferase, aspartate aminotransferase were significantly increased (P < 0.05), the level of superoxide dismutase in the liver tissue was lowered (P < 0.05), the level of malondialdehyde in liver tissue was significantly increased (P < 0.05), and liver index was increased (P < 0.05) in the model group. Pathological examination showed that there were necrosis of liver cels, fat vacuoles, fibrous tissue hyperplasia and inflammatory cel infiltration in the rats of the model group. Compared with the model group, the serum levels of hyaluronic acid, laminin, typeⅢ procolagen, typeⅣ colagen, alanine aminotransferase, aspartate aminotransferase were significantly lowered (P < 0.05), the level of superoxide dismutase in the liver tissue was significantly increased (P < 0.05), the level of malondialdehyde in the liver tissue was significantly lowered (P < 0.05), and liver index was significantly decreased (P < 0.05) in the taurine group. Pathological examination showed that there were no inflammatory cel infiltration, fat vacuoles, and fibrous tissue deposition in the liver tissue. The results indicate that taurine can decrease the contents of superoxide dismutase and malondialdehyde, and relieve the degree of liver fibrosis induced by carbon tetrachloridevia exerting its antioxidative effects.

Objective By observing the effect of Xiaoyuhuatan decoction on insulin resistance in rar with nonalchoholic fatty liver,the author made a reasearch into this herb'S machanism on cambating on nonalchoholic fatty liver.Methods The insulin resistance rat model was fed by high fat forage and Dongbaogantai control group was set up for the sake of comparion.We determined the contents of total cholesterol(TC),triglyceride(TG),free fatty acid(FFA),fasting plasma glucose(FBG),fasting serum insulin(INS)in serum and the contents of TC,TG of liver tissue homogenate of each group,and the degree of hepatocytic steatosis.Results Xiaoyuhuatan decoction could obviously decrease the index of insulin resistance and improve insulin insensitive index.Lipid in blood serum and hepatic tissues were significantly decreased,liver fat cell denaturation was improved.Conclusion The thrapentic eftect of Xiaoyuhuatan Decoction on fatty liver is probably contribute tO this herb's mechanism of improving insulin resistance and increasing insulin insensitive.

Objective:Clinicopathological features, treatment and prognosis of urinary and male reproductive system soft tissue sarcoma (STS) and sarcomatoid carcinoma in adults were compared.Methods:A retrospective analysis was performed on the clinical data of 73 patients with STS and 15 patients with sarcomatoid carcinoma in adult urinary and male reproductive system in the First Affiliated Hospital of Zhengzhou University. There were 59 males and 14 females in STS group, with a median age of 41 (18-78)years old. The maximum tumor diameter ranged from 0.5 to 19.0 cm. The primary tumors were located in testis and peritesticular (23 cases), kidney (23 cases), prostate (15 cases), bladder (8 cases), ureter(3 cases), other parts(1 case). There were 18 cases of lymph node metastasis and 8 cases of distant metastasis. Among 73 patients with STS, 66 patients underwent surgical resection, of which 31 patients underwent radical resection. Among the 66 patients who underwent surgery, 3 patients received neoadjuvant chemotherapy; 22 patients received adjuvant chemotherapy; 5 patients were treated with adjuvant radiotherapy. Among 7 patients with STS did not receive surgical treatment, 2 patients received radiotherapy combined with chemotherapy, 2 patients received chemotherapy alone, and 3 patients received symptomatic support treatment.There were 11 males and 4 females in sarcomatoid carcinoma group, with a median age of 65 (23 - 84)years old. The measurable tumor diameter ranged from 0.4 to 16.9 cm. The primary tumors were located in kidney (6 cases), bladder (5 cases), ureter(2 cases) and prostate(2 cases). There were 2 patients of lymph node metastasis and 4 patients of distant metastasis. Of the 15 patients with sarcomatoid carcinoma, 12 patients underwent surgical resection, of which 5 patients underwent radical resection. 2 patients were treated with adjuvant therapy after operation. Among the 12 patients who received surgical treatment, 2 patients had distant metastasis before operation, all of which originated from the kidney. Among the 3 patients without surgical treatment, 1 patients received systemic chemotherapy and 2 patients received symptomatic supportive treatment. There was no significant difference in gender, tumor maximum diameter, distant metastasis and operation, chemotherapy, radiotherapy and operation combined with chemotherapy ( P>0.05) and there were significant differences in age, tumor primary location and lymph node metastasis ( P<0.05) between STS and sarcomatoid carcinoma patients.The categorical variables of the two groups were compared by χ2.With Kaplan-Meier method for univariate survival analysis, the Cox was used for multivariate analysis. Results:The median follow-up time was 18.3(0.3-90.4) months.In STS group, there were 14 patients of synovial sarcoma, 11 patients of liposarcoma, 15 patients of rhabdomyosarcoma, 16 patients of leiomyosarcoma, 10 patients of other types, and 7 patients of spindle cell sarcoma without specific classification. Among 66 patients with STS, 8 patients recurred, 14 patients metastasized after operation, 4 patients recurred and metastasized after operation. The 7 patients without surgical treatment all progressed. Among the 10 patients of sarcomatoid carcinoma without distant metastasis before operation, 3 patients recurred and 3 patients metastasized after operation. Two patients of renal sarcomatoid carcinoma with distant metastasis were treated with nephrectomy and chemotherapy. One of them had overall survival (OS) up to 2 years, and one recurred 2 months after operation. The 3 patients without surgical treatment all progressed without remission. The median OS of STS patients were 59.3 (95% CI 24.1-94.5) months and that of sarcomatoid carcinoma patients were 8.7 (95% CI 6.1-11.2) months. The OS of STS patients were better than those of sarcomatoid carcinoma patients ( HR=2.874, 95% CI 1.118-7.386, P=0.022). Conclusions:The onset age of STS in adult urinary and male reproductive system was lower than that in sarcomatoid carcinoma. The primary lesions of STS were mainly in testis, peritesticular and kidney. The primary lesions of sarcomatoid carcinoma were mainly in kidney. Among STS, leiomyosarcoma was the most common type.STS and sarcomatoid carcinoma should be diagnosed and treated with surgery quickly, and systemic therapy should be performed for patients who cannot be treated with surgery.

OBJECTIVETo explore the relationship between interleukin-6 (IL-6) production and central nervous injury in septic patients.

METHODSTwenty-two septic patients without central nervous system diseases were examined for serum IL-6 and neuron-specific enolase (NSE) levels, and the serum NSE levels and APACHEII scores were compared between patients with low, moderate, and high serum IL-6 levels. The correlations between NSE, APACHEII and serum IL-6 were analyzed.

RESULTSIn patients with low, moderate, and high serum IL-6 levels, the serum levels of NSE were 10.29∓4.05, 16.06∓5.84 and 23.97∓3.28 µg/L, respectively, showing a significant difference between the 3 groups (P<0.001). The APACHEII scores also differed significantly between the 3 groups (14.17∓4.67, 16.40∓4.84, and 24.00∓6.26, respectively, P=0.009). Correlation analysis showed significant positive correlations of IL-6 with NSE (r=0.788, P<0.001) and with APACHEII scores (r=0.733, P<0.001).

CONCLUSIONIn septic patients, serum IL-6 level is significantly correlated with the severity of sepsis and brain injury, and can be used as a marker to monitor brain injury in septic patients.

APACHE ; Adult ; Aged ; Brain Injuries ; blood ; pathology ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Phosphopyruvate Hydratase ; blood ; Sepsis ; blood

A patient with skin rash, skin denudation, anuria, general dropsy and dyspnea for unknown etiology underwent continuous renal replacement therapy (CRRT) for 3 consecutive days. The biochemical indexes were monitored during the therapy and biopsy was performed on the right thigh. Pathological examination of the biopsy sample established the diagnosis of polymyositis(PM) and dermatomyositis(DM). After the start of CRRT, the patient's heart, liver, kidney and lung injuries showed obvious improvement, and the urine volume (UV) increased and serum creatinine (Cr), urea, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) levels all decreased promptly. The patient showed progressive improvement of the physiological condition even after CRRT, and was discharged 10 days later. This case suggests the efficacy of CRRT in the management of severe PM/DM and its value as a good option for treatment of severe autoimmune disease, especially systemic inflammatory response syndrome.
Adult ; Dermatomyositis ; therapy ; Humans ; Male ; Polymyositis ; therapy ; Renal Replacement Therapy ; Treatment Outcome

Objective:To compare the efficacy of HES 130/0.4 and acetate Ringer′s solution (A-HES) and HES 130/0.4 and normal saline (NS-HES) for volume therapy in the patients undergoing non-cardiac surgery with general anesthesia.Methods:Two hundred and fifty American Society of Anesthesiologist physical status Ⅰ or Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 18-32 kg/m 2, undergoing noncardiac surgery with general anesthesia, were divided into group A-HES and group NS-HES using the stratified block randomization technique.A-HES and NS-HES 15 ml/kg were intravenously infused over 1 h immediately after induction of anesthesia in A-HES and NS-HES groups, respectively.Mean arterial pressure (MAP), heart rate (HR) and central venous pressure (CVP) were recorded before and after infusion, and the maximum changing rate of MAP and HR and the maximum change in CVP were calculated.The pH value, BE and HCO 3- were recorded before infusion and at 15 min after the end of infusion, and Hb, Hct, electrolytes, blood glucose, blood biochemical parameters and parameters of coagulation function were measured.The occurrence of abnormal blood biochemical parameters, blood glucose, and parameters of coagulation function, intraoperative requirement for vasoactive drugs, occurrence of HES-related adverse events, and intraoperative fluid intake and output were recorded. Results:A total of 251 cases were actually enrolled in this study, with 125 cases in group A-HES, and 126 cases in group NS-HES.Compared with group NS-HES, no significant change was found in the maximum changing rate of MAP and HR and the maximum change in CVP ( P>0.05) in group A-HES, and non-inferiority analysis showed that group A-HES was not inferior to group NS-HES.Compared with group NS-HES, the concentrations of BE and HCO 3-, K + , Ca 2+ and Mg 2+ were significantly increased, the concentrations of Na + and Cl - were decreased, the PT was shortened, the incidence of abnormal PT was decreased at 15 min after the end of infusion ( P< 0.05), and no significant change was found in the other parameters mentioned above in group A-HES ( P>0.05). Conclusion:The volume expanding effect of A-HES and its effect on liver and kidney function are not significantly different from those of NS-HES, however, A-HES has certain advantages in maintaining acid-base balance, electrolyte stability and coagulation function.

Objective:To study the role of special microbial communities in the development of periodontitis in type 2 diabetes melli-tus(T2DM)patients.Methods:40 subjects aged 20-70 years were included and divided into 3 groups:moderate to severe periodon-titis with T2DM(SP.T2DM,n=15),moderate to severe periodontitis group(SP,n=15)and normal healthy group(N,n=10).The basic information,periodontal clinical indicators and blood sugar of the subjects were recorded.Subgingival plaque samples were col-lected,DNA samples of the plaque were extracted,and sequenced by Illumina NovaSeq6000 platform.The microbial diversity,eco-logical characteristics and functions of the plaque were analyzed by Uparse,SPSS and other softwares.Results:481 species in 22 phyla,30 classes,73 orders,129 families and 265 genera were obtained from the samples.Beta polymorphism analysis showed that the species composition of CP.T2DM group and CP group was similar.Alpha polymorphism analysis showed that the species richness and evenness in CP.T2DM group and CP group were higher than those in N group(P＜0.01).Venn diagram analysis showed that the species richness of the plaque in CP.T2DM group was the highest,followed by CP group and the lowest in N group.At the genus lev-el,Klebsiella and Bifidobacterium in CP.T2DM group were larger than those in CP group and N group(P＜0.05),and between group CP and N,P＞0.05.At the species level,the Capnocytophaga leadbetteri in CP.T2DM group was higher than that in CP group and N group(P＜0.05),between group CP and N,P＞0.05;There were some differences in the microbial community structure of subgingival plaque among the 3 groups.The species richness of subgingival flora in patients with CP and T2DM was higher than that in patients with CP and healthy people.Conclusion:The increase of Klebsiella,Bifidobacterium and Capnocytophaga leadbetter in subgingival flora of patients with moderate and severe periodontitis may be related to the development of T2DM.

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.
Nucleic Acids ; RNA, Small Interfering/genetics* ; Drug Carriers ; Drug Delivery Systems ; Drug Development

Objective:To find the biomarkers that accurately predict the survival of patients with esophageal squamous cell carcinoma (ESCC).Methods:The immune related genes that were significantly related to the overall survival (OS) of patients with ESCC were screened from The Cancer Genome Atlas (TCGA) database to construct a prognostic risk score model. The prognoses of the high-risk and low-risk groups were compared by Kaplan-Meier method. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve. Tumor tissue samples of 83 patients with pathological diagnosis of ESCC were collected from Anyang Cancer Hospital for external verification. Cox regression analysis was used to comprehensively evaluate the effects of prognostic risk score and various clinical characteristics on OS of patients with ESCC.Results:Seven immune-related genes that were significantly related to survival prognosis were selected from the TCGA database and included in the prognostic risk score model, which were S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2. The 1- and 2-year survival rates of the low-risk group (40 cases) were 94.3% and 82.5%, respectively, while those of the high-risk group (40 cases) were 75.9% and 32.9%, respectively.The prognosis of the high-risk group was worse than that of the low-risk group ( P<0.001). The 83 external validation samples obtained consistent results by using the prognostic risk score model. The prognostic risk score was positively correlated with the content of CD4 + T lymphocytes in ESCC ( rs=0.259, P=0.020), but not correlated with the content of B lymphocytes, CD8 + T lymphocytes, neutrophils, macrophages or dendritic cells ( P>0.05). Conclusions:S100A12, SLC40A1, FABP9, TNFSF10, IGHA2, IL1F10, and STC2 were risk genes significantly associated with OS of patients with ESCC. The prognostic risk score was an independent prognostic factor for the OS of patients with ESCC, and it was correlated with the content of CD4 + T lymphocytes in ESCC tissue.