This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN). METHODS: Related test results of 283 newborns and their mothers' blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil). RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility ［75.45%(126/167)］, followed by O/B incompatibility［54.55%(60/110)］. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the "direct antibody+indirect antibody+release+" group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants. CONCLUSION ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.
Humans ; Infant, Newborn ; ABO Blood-Group System ; Erythroblastosis, Fetal/epidemiology* ; Female ; China/epidemiology* ; Blood Group Incompatibility ; Male ; Bilirubin/blood*

Objective To investigate the correlation between c-MYC expression and mitochondrial metabolism in malignant duct epithelial cells of pancreatic cancer patients.Methods GEPIA database was used to analyze the correlation between c-MYC expression and overall survival.The expression of c-MYC in tumor tissues was detected by immunohistochemical staining.The difference of DLAT and DLST gene expression between tumor and normal tis-sues was compared in GEPIA database.HP A database was used to analyze the correlation between c-MYC and DLAT,DLST expression in tumor tissues.The expression level of DLAT and DLST in tumor tissues was evaluated by immunofluorescence staining.Results The high expression of c-MYC gene was negatively correlated with overall survival(P＜0.01).The level of c-MYC protein was positively correlated with the pathological grade of PanIN.Compared with normal tissues,the expression of DLAT and DLST genes in pancreatic cancer cells was increased(P＜0.01).The protein level of c-MYC was positively correlated with those of DLAT and DLST(P＜0.01,P＜0.001).Conclusions The high expression of mitochondrial metabolic enzymes DLAT and DLST in pancreatic ductal adenocarcinoma cells is significantly correlated with the expression level of c-MYC,which increases with the progression of pancreatic cancer.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

AIM To study the amino acids and proteins in 16 batches of commercial fish swim-bladders with different origins.METHODS A high performance liquid chromatography method based on pre-column derivatization using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate(AQC)was developed for the determination of contents and components of 17 amino acids in fish swim-bladders.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was performed to analyze the molecular weight distribution of proteins from different fish swim-bladders,and proteins in fish swim-bladders were identified by proteomics method.RESULTS The result showed that the determination of 17 amino acids had a good linear relationship(R2≥0.998 0).The average recovery rate was 85.62%-109.60%and the relative standard deviations of precision,stability and repeatability were less than 3.5%.The total content of the 17 amino acids in 16 batches of fish swim-bladders ranged from 468.31 mg/g to 620.05 mg/g.A total of 688 proteins including 11 collagens were identified from 16 batches of fish swim-bladder samples and a plenty of low-abundance proteins at 52-95 kDa were also detected in fish swim-bladders by SDS-PAGE.CONCLUSION This study provides a good reference for the quality evaluation and further utilization of fish swim-bladders.

Objective To observe the therapeutic efficacy and mechanism of Gushi Zaizao Pills for steroid-induced osteonecrosis of the femoral head(SONFH).Methods Male SD rats were randomly divided into normal group,model group,Xianling Gubao Capsules group and Gushi Zaizao Pills group.Except for the normal group,the rats in all other groups were replicated the SONFH model.After successful modeling,the continuous drug administration was carried out for six weeks.The thymus and spleen of the rats were taken to calculate the immune organ indices,the contents of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in rat synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA),the percentage of empty lacunae and area ratio of trabecular bone was detected by hematoxylin-eosin(HE)staining,and the femoral head parameters[reduction of bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)]were analyzed by Micro-CT,and bone strength of femoral head was detected by small animal bone strength tester.Results Compared with the normal group,the spleen and thymus indicators were significantly decreased in the model group,the levels of IL-1β and TNF-α in rat synovial fluid were significantly increased,the percentage of empty lacunae was increased,the area ratio of trabecular bone was decreased,the BV/TV,Tb.N and Tb.Th were decreased,the Tb.Sp was increased,the bone strength of femoral head was significantly decreased,the differences being all statistically significant(P＜0.05 or P＜0.01).Compared with the model group,the spleen and thymus indicators were significantly increased in Xianling Gubao Capsules group and Gushi Zaizao Pills group,the levels of IL-1β and TNF-α in rat synovial fluid were decreased,the percentage of empty lacunae was significantly decreased,the area ratio of trabecular bone was significantly increased,the BV/TV,Tb.N and Tb.Th were increased,the Tb.Sp was decreased,and the bone strength of femoral head was significantly increased,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Gushi Zaizao Pills can effectively prevent the further development of SONFH by regulating cellular immunity and reducing the secretion of inflammatory factors,thereby reducing the pathological damage of the femoral head and enhancing the bone strength.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

AIM: To explore the feasibility of swept source optical coherence tomography angiography(SS-OCTA)in evaluating early retinal and choroidal microcirculation changes in patients with hypertension.METHODS:Prospective clinical study. A total of 27 patients with grade 2 or 3 essential hypertension(hypertension group)diagnosed in the Department of Cardiology of Xi'an First Hospital from July to November 2022 were included in the study. There were 14 males and 13 females. The mean age was(57.11±3.36)years. During the same period, 27 age- and sex-matched normal people without a history of hypertension were selected as the control group, including 12 males and 15 females. The average age was(55.74±2.95)years old. All patients underwent BCVA(LogMAR), intraocular pressure, axial length, slit lamp examination, fundus color photography and SS-OCTA examination. SS-OCTA was used to scan the macular area of the right eye in the range of 6×6 mm. The retina and choroid were divided into three concentric circles with diameters of 0-1 mm, 1-3 mm and 3-6 mm around the fovea according to ETDRS. Macular vessel density(VD), perfusion area(PA), retinal thickness(CMT), choroidal thickness(CT), choroidal vessel volume(CVV)and choroidal vasculr index(CVI)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular area of 0-1 mm, 1-3 mm and 3-6 mm were analyzed and recorded. The changes in VD, PA, CMT, CT, CVV and CVI were compared between the two groups. Independent sample t-test was used to compare VD, PA, CMT and CVI between the two groups; CT, CVV and LogMAR visual acuity were analyzed by Wilcoxon signed rank test of independent samples.RESULTS:Compared with the control group, the hypertensive group had significantly lower VD in the macular area 0-3 mm(0-1 mm, t=-3.144; 1-3 mm, t=-3.611, P<0.05). VD in the area of 3-6 mm showed a tendency to increase compared with the control group(t=1.715, P>0.05). The CMT in the 0-1mm area of the macular area in the hypertension group was lower than that in the control group(t=-2.624, P<0.05). There was no significant difference in CT, CVV and CVI between the two groups(P>0.05).CONCLUSION:The VD of DCP in the 0-3 mm area and the CMT in the 0-1 mm area are decreased in hypertensive patients. There were no significant differences in CT, CVV and CVI between the two groups. VD and CMT in macular DCP may be used as indicators to evaluate the early changes of retinal and choroidal microcirculation in hypertensive patients.

Objective To discuss the effect of Anemarrhenae Rhizoma with different proportions on the dissolution of 6 inorganic elements(K,Ti,Sr,Ba,Ca,Mg)in Gypsum Fibrosum under different compatibility based on grey correlation analysis and technique for order preference by similarity to an ideal solution(TOPSIS)method and to provide reference for clinical application.Methods Inductively coupled plasma mass spectrometry(ICP-MS)was established for simultaneous analysis of inorganic elements K,Ti,Sr,Ba,Ca,Mg in Gypsum Fibrosum-Anemarrhenae Rhizoma.The gray correlation ananlysis and TOPSIS method were used to comprehensively analyze the changes of six inorganic elements in Gypsum Fibrosum under different compatibility.Results The findings of the ICP-MS determination of inorganic elements in Gypsum Fibrosum-Anemarrhenae Rhizoma were good in terms of linearity,precision,repeatability and stability.The average recovery was 81.78％-104.13％,and the RSD was 2.10％-4.62％(n=6).The dissolution of six inorganic elements in Gypsum Fibrosum after compatibility with different proportions of Anemarrhena Rhizoma was significantly higher than that of Gypsum Fibrosum single decoction(P＜0.05).The dissolution scores of six inorganic elements in Gypsum Fibrosum were the highest when the compatibility proportion of Gypsum Fibrosum-Anemarrhenae Rhizoma was 30∶9.Conclusion ICP-MS is a sensitive and accurate method for determining K,Ti,Sr,Ba,Ca and Mg in Gypsum Fibrosum-Anemarrhenae Rhizoma.The best compatibility ratio of Gypsum Fibrosum-Anemarrhenae Rhizoma is 30:9,which can effectively improve the dissolution of six inorganic elements in Gypsum Fibrosum,and provide the basis for the further compatibility study of Gypsum Fibrosum and Anemarrhenae Rhizoma.