Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

【Objective】 To study the incidence and specificity of platelet antibody in blood donors in Suzhou, analyze the distribution characteristics of platelet antibody in blood donors in this area, and explore the significance of platelet antibody detection in blood donors to reduce the adverse reactions toplatelet transfusion in clinical. 【Methods】 Platelet antibody detection was performed in 2178 blood donors in this area by solid-phase immunosorbent assay. The antibody specificity of the positive samples was analyzed by commercial kit, and the anti-CD36 antibody positive samples were further identified by flow cytometry and gene sequencing. 【Results】 Twelve positive samples were detected by platelet antibody screening, with a positive rate of 0.55%(12/2 178), including 5 males (0.33%, 5/2 178)and 7 females(1.06%, 7/2 178). Among the positive samples, anti-HLA-Ⅰ antibody was identified in 2 cases, anti-CD36 antibody in 1 case, and the antibody specificity was not identified in the other 9 cases. In one case, the positive rate of anti-HLA-Ⅰ antibody PRA was 31.31%(31/ 99), which was mainly specific to anti-B15, anti-B35 and anti-B40. The positive rate of anti-HLA-Ⅰ antibody PRA in the other case was 45.45%(45/ 99), which was mainly specific to anti-A2, anti-A11, anti-A24, anti-A29, anti-A33, anti-A66, anti-B15 and anti-B35. The blood donor with anti-CD36 antibody was type I CD36 deficiency, and 329_330delAC mutation occurred in exon 5. 【Conclusion】 Through antibody screening and specificity identification, the positive rate of platelet antibody in females was significantly higher than that in males(P<0.05). In addition to the common anti-HLA-I antibodies, anti-CD36 antibody was also detected in type I CD36 deficient blood donor. Therefore, the detection of platelet antibodies in blood donors is of certain clinical significance to reduce the adverse reactions to blood transfusion caused by antibodies in platelet products.

Objective To explore the correlation between the pathogenesis of coronary heart disease and the polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) .Methods 130 cases of coronary heart disease diagnosed and treated in Heze Municiple Hospital from July 2015 to July 2017 were selected as observation group .At the same time,130 healthy people were selected as control group .The serum folate and homocysteine ( HCY) levels were compared between the two groups .At the same time, polymerase chain reaction -restriction fragment length polymorphism was used to analyze the MTHFR gene polymorphisms .The distribution of MTHFR gene polymorphism was compared between the two groups .Results The level of serum folic acid in the observation group was (5.76 ± 2.14)g/L,which was significantly lower than (7.34 ±2.43)g/L in the control group (t=5.64,P<0.05).The level of serum HCY in the observation group was (15.46 ±5.74)μmol/L,which was significantly higher than (10.28 ± 4.38)μmol/L in the control group (t=6.43,P<0.05).The frequencies of TT type,TC type and CC type of MTHFR gene in the observation group were 36.92％,46.92％and 16.15％,respectively.The frequencies of TT type,TC type and CC type of MTHFR gene in the control group were 21.54％,55.38％ and 23.08％,respectively.The frequency of TT type in the observation group was significantly higher than that of the control group (χ2 =8.25,P<0.05). There were no statistically significant differences in folic acid levels among different gene types in the observationgroup(t=1.31,0.55,0.73,all P>0.05),but the serum HCY level of TT type was significantly higher than that of CT type and CC type in the observation group (t=5.33,4.62,all P<0.05).Conclusion Serum folic acid level, HCY level and homozygous mutations of MTHFR gene type have certain relationship with the occurrence of coronary heart disease ,the body serum folic acid level and the distribution of MTHFR genotypes can affect the concentration of HCY,thus affecting the occurrence of coronary heart disease .

Objective To study the prevalence and related risk factors of type 2 diabetes with coronary heart disease(CHD) and cerebral infarction after long-term treatment.Methods Two hundred and eighty-five patients with type 2 diabetes who had a hospitalization interval for four to twelve years between the first and second hospital stays were included in group A.Among them,85 patients (about 4 to 7 years) with a hospitalization interval about 5 years (4 to 7 years) between the first and second hospital stays(group B).100 patients with a hospitalization interval about 10 years (8 to 12 years) between the first and second hospital stays(group C).Blood pressure,blood glucose,HbA1c,blood lipids,myocardial enzymology,electrocardiogram,coronary angiography,cranial CT or MRI were tecorded.The prevalence of CHD and cerebral infarction were compare,regression analysis was conducted between coronary heart disease,cerebral infarction and the risk factors.Results DBP,FBG,PBG2h,TC,LDL-C of the second hospitalization were significantly lower than those of the first hospitalization.The morbidity of CHD and cerebral infarction increased along with the extension of the course.The morbidity of cerebral infarction in CHD patients were significantly higher than those in non-CHD patients with the interval about 10 years.Logistic regression analysis proved that age was risk factor and HDL-C was protective factor of CHD,SBP,FBG were risk factors of cerebral infarction.Conclusion The morbidity of CHD and cerebral infarction increased along with the extension of the course and there were significantly relationship between CHD and cerebral infarction in T2DM patients after about 10 years treatment.

Objective To explore the relationship between the levels of plasma coagulation factors (F) and acute myocardial infarction (AMI) in low age period (<60 years old) and their diagnostic value in diagnosing AMI in low age period.Methods One hundred and sixty inpatients with low age AMI in the cardiology department of the Heze Municipal Hospital were selected as the case group,and contemporaneous 160 cases of low age non-AMI served as the control group.F Ⅱ,FⅦ,FⅧ,fibrinogen (Fg) and von willebrand (vWF) were measured with enzyme-linked immunoabsorbent anti-sandwich assay.The relationship between coagulation factors and low age AMI was analyzed with univariate and multivariate analysis,and their value for diagnosing low age AMI was evaluated with diagnostic test and receiver operating characteristics (ROC) curve.Results The univariate analysis showed that FⅡ,FⅦ,FⅧ and Fg levels had significantly statistical difference between the case group and control group(P<0.05),and the vWF level had no statistically difference(P>0.05).The multivariate analysis indicated that the FⅡ level≥ 14.27 μg/L and FⅦ level ≥22.99 μg/L were the independent risk factors for low age AMI.The value of FⅡ for diagnosing low age AMI was lower,and the optimal cut off value of Fg for diagnosing low age AMI was 22.99 μg/L,its area under ROC curve was 0.709 with a moderate diagnostic value,and the sensitivity (91.88%) and negative predictive value (86.02%) were higher,the false negative rate (13.98%) was lower,and the accuracy (70.94%) was moderate.Conclusion The FⅡ level ≥14.27 μg/L and Fg level ≥22.99 μg/L are the independent risk factors for low age AMI,and detecting the Fg level could have hint significance in diagnosing low age AMI.

Objective To discuss clinical curative effects of using Forehead skin expansion combine with auricular cartilage for repairing nose alar full-thickness defects.Methods From August 2010 to August 2010,36 patients with nose alar full-thickness defects in the second affiliated hospital of kunmin medical university,The defect range exceed 1.5 cm× 1.2 cm.50-80 ml expander was implanted in forehead and injected saline water to expand in order to acquire extra skin.We Turn around the skin of defect as the lining of nose,harvest ipsilateral auricular cartilage for nose ala framework,Expanded forehead pedicle flap was transferred to cover framework.The donor area was sutured directly.The pedicle of flap was cut and trimmed after 2 months.Results Follow-up time of 3-18 months after the operation,All flaps are survive,nose alar defects are repaired successfully.Some cases were performed second surgery,postoperative,nose alar color,thickness,nostril size and shape the same with the contralateral side.Donor site healed with linear scar.Conclusions This method could be easy to obtain excess skin,for repairing large sides nose alar full-thickness defect.Frontal scar is not obvious,It is a practical.

Background and objective It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that con-tain high levels of polycyclic aromatic hydrocarbons. Tis risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County. Methods On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking his-tory, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the associa-tion between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Sofware. Results Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3). Tere was marked heterogeneity in risk estimates for specific sub-types of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. Te GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G) genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9 (1.1-3.3), re-spectively. Compared to subjects who with GSTM1-positive and used less than 130 tons of smoky coal during their lifetime, higher risks were closely associated with GSTM1-null and heavier users (≥130 tons), with the OR was 4.9 (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively. However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2), respectively. Conclusion Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. Te GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly associated with higher risk of lung cancer, especially among heavily exposed women.

OBJECTIVETo investigate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on the stability of resin-dentin bonds against pH cycling.

METHODSResin-bonded dentin specimens were prepared following manufacturers' instructions, and randomly divided into 3 groups. Among them, 2 groups experienced pH cycling, in which specimens applied CPP-ACP or distilled and deionized water (DDW) on the bonding interface, respectively. Microtensile bond strength (muTBS) testing, failure mode analysis, micromorphological and nanoleakage evaluation of bonding interface and elemental analysis within hybrid layer were performed after 15 days pH cycling. The other group was tested immediately after specimens' preparation without pH cycling.

RESULTSNo significant differences were found in muTBS between no pH cycling and pH cycling/CPP-ACP group. Their muTBS were both significantly higher than that of pH cycling/DDW group (P < 0.05). Mixed fractures were the most prevalent failure mode. The quality of hybrid layer in pH cycling/CPP-ACP group was better than that of pH cycling/DDW group, and the nanoleakage was also less severe. Comparing with pH cycling/DDW group, the atomic percentages of Ca in the other two groups were both significantly higher, while those of Ag were statistically lower (P < 0.05).

CONCLUSIONLocal application of CPP-ACP can promote the stability of resin-dentin bonding interface against pH cycling and prolong bonding degeneration.