Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To analyze the B_el subtype gene mutation and its genetic mechanism in a family line. METHODS: ABO blood groups were identified by serologic tests. ABO genotyping was performed by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sanger sequencing was performed on exons 1-7 of the ABO gene, the flanking intronic region, and exon 7 of the single strand of the gene confirmed the mutation site location. Missense3D software was used to predict the protein structure alteration caused by this mutation. RESULTS: Conventional serologic tests failed to detect erythrocyte B antigen in the proband and her three family members, and only trace amounts of B antigen expression could be detected by the absorption-dispersal test. DNA analysis showed that, on the basis of the normal ABO gene, there was a G>T substitution in the position of exon 7, position 803, which resulted in the change of amino acid 268 from Gly to Val. Further single-stranded sequencing analysis showed that the mutation site was located in the B gene. CONCLUSION In this family line, the proband, her father, her son, and her daughter all have reduced B type glycosyltransferase activity due to the new point mutation (c.803G>T) in exon 7 of the B gene, and the B antigen can only be detected by the absorption-dispersal method, and the point mutation can be stably inherited by offspring.
Point Mutation ; Alleles ; ABO Blood-Group System/genetics* ; Exons ; Introns ; Genotype ; Humans ; Male ; Female ; Glycosyltransferases/genetics*

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies,in order to provide reference for clinical infection control and treatment.Methods:The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed.They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation.The types of pathogens and their drug resistance were analyzed.Results:Two hundred and ninety-nine positive strains of pathogenic bacteria were detected.In the transplantation group,Gram-negative bacteria accounted for 68.5％(50/73),Gram-positive bacteria accounted for 6.8％(5/73),and fungi accounted for 24.7％(18/73).The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8％,and 11.5％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0％,and 56.2％to carbapenems.In the non-transplantation group,Gram-negative bacteria accounted for 64.1％(145/226),Gram-positive bacteria accounted for 31.0％(70/226),and fungi accounted for 4.9％(11/226).Gram-positive bacteria were mainly Enterococcus faecium(6.6％,15/226)and Coagulase-negative Staphylococci(6.2％,14/226).The fungi were all Candida tropicalis.The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8％,and 10.3％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3％,and 26.8％to carbapenems.Conclusion:The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied.Gram-negative bacteria is the main pathogenic bacteria.The resistance of pathogenic bacteria to antibiotics is severe.Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Objective:To observe the changes of 5-hydroxytryptamine (5-HT) level in myocardial tissue of pre-treatment mice with sepsis myocardial injury by electroacupuncture at Zusanli point, and to explore the protective effect and possible mechanism of electroacupuncture on myocardial injury in sepsis.Methods:Twenty male C57BL/6 mice were divided into control group (NC group), sepsis model group (LPS group), electroacupuncture group (EA group) and electroacupuncture + fluoxetine group (EA+FLU group) by random number table method, with 5 mice in each group. The myocardial injury model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 g/L. The NC group was intraperitoneally injected with the same amount of normal saline. 3 days before mold making, EA group and EA+FLU group were electrocuted at Zusanli point on both sides for 15 minutes, once a day for 3 days. The EA+FLU group was intraperitoneally injected fluoxetine 1.4 g/L before electroacupuncture. After modeling, the cardiac histopathological changes were observed by hematoxylin-eosin (HE) staining. The serum levels of inflammatory cytokines interleukins (IL-6, IL-8), and tumor necrosis factor-α (TNF-α), the content of 5-HT in myocardial tissue, myocardial injury markers MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTnI), and the levels of adenosine triphosphate (ATP) and lactic acid in myocardial tissue were detected. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of 5-hydroxytryptamine transporter (5-HTT), hexokinase 2 (HK2) and glucose transporter 4 (GLUT4) in myocardial tissue. GLUT4 expression in myocardial tissue was detected by immunofluorescence assay.Results:Compared with NC group, the serum levels of IL-6, IL-1β and TNF-α, myocardial 5-HT content, myocardial tissue injury markers CK-MB, cTnI in LPS group and EA+FLU group were significantly increased. Compared with LPS group, the above indexes in EA group were significantly decreased [IL-6 (ng/L): 443.03±156.16 vs. 19?843.75±0.00, IL-1β (ng/L): 75.72±10.60 vs. 894.66±350.88, TNF-α (ng/L): 46.17±4.71 vs. 533.01±170.58, 5-HT (μg/L): 161.19±5.96 vs. 244.74±14.38, CK-MB (ng/L): 468.21±12.46 vs. 662.02±22.54, cTnI (ng/L): 0.83±0.05 vs. 0.99±0.08, all P < 0.05]. Compared with NC group, the levels of ATP in myocardium of LPS group, EA group and EA+FLU group were significantly decreased, the levels of lactic acid in myocardium were significantly increased. Compared with LPS group, the level of ATP in myocardium of EA group was significantly increased, the level of lactic acid in myocardium was significantly decreased [ATP (mmol/L): 0.10±0.01 vs. 0.08±0.01, lactic acid (mmol/L): 56.03±1.07 vs. 72.45±4.32, both P < 0.05]. Compared with NC group, the mRNA expression of HK2 in myocardium of LPS group was significantly increased, and the mRNA expressions of GLUT4 and 5-HTT were significantly decreased. Compared with LPS group, the mRNA expression of HK2 in myocardium of EA group was significantly decreased, the mRNA expressions of GLUT4 and 5-HTT were significantly increased [HK2 mRNA (relative expression level): 0.73±0.19 vs. 1.82±0.57, GLUT4 mRNA (relative expression level): 1.00±0.33 vs. 0.47±0.18, 5-HTT mRNA (relative expression level): 1.18±0.31 vs. 0.38±0.15, all P < 0.05]. Compared with NC group, the fluorescence intensity of GLUT4 in LPS group and EA+FLU group were significantly decreased. Compared with LPS group, the fluorescence intensity of GLUT4 in EA group was significantly enhanced. Conclusions:Electroacupunctureat Zusanli can reduce the content of 5-HT in myocardial tissue of sepsis mice, and its regulatory mechanism may be related to the regulation of 5-HTT and GLUT4.

Objective To observe the effects of Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol on lowering blood pressure and improving hemorheology in patients with gestational hypertension.Methods Ninety patients with gestational hypertension of liver-yang hyperactivity type were randomly divided into the combination group and the control group,with 45 cases in each group.The control group was treated with magnesium sulfate combined with Labetalol,and the combination group was treated with Tianma Gouteng Decoction on the basis of treatment for the control group.The course of treatment lasted for 5 days.The changes of systolic blood pressure(SBP),diastolic blood pressure(DBP),urinary protein level,and hemorheological indicators of the two groups were observed before and after the treatment.Moreover,the adverse pregnancy outcomes,adverse reactions,and patients'satisfaction of the two groups were compared.Finally,the influencing factors of patients'adverse pregnancy outcomes were investigated by logistic regression analysis.Results(1)After treatment,the SBP,DBP and urinary protein level of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the hemorheological indicators of plasma viscosity,whole blood viscosity and hematocrit of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the combination group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)The total incidence of adverse pregnancy outcomes in the combination group was 11.11%(5/45),which was significantly lower and that in the control group(33.33%,15/45),the difference being statistically significant(P＜0.05).(4)The patients'satisfaction of the combination group was 97.78%(44/45),which was significantly higher than that of the control group(84.44%,38/45),and the difference was statistically significant(P＜0.05).(5)The total incidence of adverse reactions in the combination group was 13.33%(6/45)and that in the control group was 8.89%(4/45),but the intergroup comparison showed no significant difference between the two groups(P＞0.05).(6)Logistic regression analysis of influencing factors showed that no medication of Tianma Gouteng Decoction combined with Labetalol and magnesium sulfate,and poor antihypertensive effect were the independent risk factors for adverse pregnancy outcomes in patients with gestational hypertension(all OR＞1,P＜0.05).Conclusion Tianma Gouteng Decoction combined with magnesium sulfate and Labetalol in treating gestational hypertension exerts certain antihypertensive effect,and the therapy can effectively improve the hemorheological indicators and the adverse pregnancy outcomes,and enhance the patients'satisfaction.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.