Objective To analyze medication patterns and the targets and pathways of core drug combinations in treatment of palpitation.Methods The prescriptions of Li Yaping for treatment of palpitation from March 2023 to March 2024 were collected,and frequency counts of drugs'nature and flavour,channel tropism,and efficacy were performed.Apriori algorithm,association rules,and clustering analysis were carried out using SPSS Modeler 18.0 and SPSS 26.0.The core drugs and disease targets were searched,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the targets of their therapeutic action for palpitation.Results A total of 220 prescriptions were collected,involving 192 flavors of traditional Chinese medicines,with a cumulative medication frequency of 3978 times,and 18 flavors of high-frequency medicines.The medicines were mainly tonics,sedative,and promoting blood circulation for removing blood stasis.The distribution of medicinal properties were mainly warm,cold and flat.The medicinal flavors were mainly sweet,bitter and pungent,and channel tropism were mostly heart,liver and spleen channel.Association rule analysis showed that Radix Angelicae Sinensis,Radix et Rhizoma Salviae Miltiorrhizae,Radix et Rhizoma Glycyrrhizae,Radix Ophiopogonis,and Radix Astragali were the core drugs.Cluster analysis showed that there was 3 cluster combinations.In the network pharmacology part,there were 181 targets intersected by drug combinations and diseases.KEGG analysis showed that the core drugs for palpitation mainly involved signaling pathways such as phosphoinositide 3-kinase/protein kinase B,hypoxia-inducible factor-1,mitogen-activated protein kinase,interleukin-17,etc.GO analysis obtained 1000 GO pathways,of which 760 were biological processes,93 were cellular components,and 147 were molecular functions.Conclusion In the treatment of palpitation,Li Yaping advocates benefiting qi and promoting yang,removing blood stasis and eliminating turbidity,and tranquilizing the mind,emphasizing the"two hearts in the same adjustment",and treating the heart and liver at the same time,taking into account the spleen and stomach,and the combination of core medicines can intervene in the course of palpitation through multi-components,multi-targets,and multi-pathways,which is of great significance for the treatment of palpitation in the clinical setting.

Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.

【Objective】 To study the role and mechanism of sinomenine in the macrophage polarization induced by gastric cancer cells. 【Methods】 Sinomenine was added to gastric cancer cells BGC-823 and MKN-45， cell viability was measured by CCK-8， cell proliferation was measured by colony formation experiment， Co-culture and Transwell cell migration experiments were used to evaluate the recruitment and polarization of macrophages by sinomenine， flow cytometry was used to evaluate the polarization of macrophages， and qRT-PCR and Western blot were used to detect the expression of gene RNA and protein levels. 【Results】 Sinomenine could inhibit the proliferation of gastric cancer cells and the recruitment of gastric cancer cells to macrophages， thus promoting macrophage M2 polarization. It simultaneously inhibited the expression of STAT6 as well as the expression and phosphorylation of C/EBPβ. When STAT6 is overexpressed， it could reduce these inhibitory effects of sinomenine on gastric cancer cells. Further research found that STAT6 mediated the secretion of IL-6 by gastric cancer cells， which was the cause of sinomenine-mediated macrophage recruitment and M2 polarization. 【Conclusion】 The natural drug sinomenine has a good tumor-suppressing ability against gastric cancer， directly inhibits the survival and migration of gastric cancer cells， and inhibits the expression of IL-6 and the M2 phenotype in the tumor microenvironment， reshapes the tumor environment， and reduces the risk of M2 type macrophages for gastric cancer tumors.

Maturity-onset diabetes of the young 3 (MODY3) is an autosomal dominant monogenic diabetes mellitus characterized by defective β-cell function and non-insulin-dependent early-onset diabetes mellitus. The facts that patients with MODY3 are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive, make its diagnosis very challenging. In this study, we reported a case of MODY3, which was verified to be caused by a mutation in hepatocyte nuclear factor 1α gene (c.598C>T, p.Arg200Trp). In addition, the patient had a neuroendocrine tumor simultaneously, and a KMT2D gene mutation (c.5587C>G, p.Pro1863Ala) might be associated with this leson.

【Objective】 To investigate the effects of RASSF6 gene on gastric cancer cells’ proliferation， autophagy， apoptosis， and sensitivity to oxaliplatin chemotherapy. 【Methods】 Gastric cancer BGC823 cells were cultured in vitro and divided into experimental control group （control group）， RASSF6 overexpression group （Oe group）， RASSF6 interference group， and lentivirus control group according to the expression effect of lentivirus gene. The changes in cell proliferation， cell cycle distribution， cell migration， autophagy， apoptosis and sensitivity to oxaliplatin in each group were detected， and the number of autophagy bodies in each group was detected by electron microscopy. Real-time PCR （qRT-PCR） and Western blotting were used to detect the expression levels of apoptosis- and autophagy-related genes in each group. 【Results】 Studies on the biological behavior of gastric cancer BGC823 cells induced by RASSF6 gene expression showed that compared with the control group， the percentage of G0/G1 phase cells in the Oe group increased， while the percentage of G2 and S phase cells decreased， with statistical significance （P<0.05）. The apoptosis rate was significantly increased （P<0.05）. The cell scratch assay showed that the scratch healing rate was significantly decreased （P<0.05）. Studies on the sensitivity of RASSF6 gene expression to oxaliplatin showed that compared with the drug group （L-OHP group）， the apoptosis rate of Oe+L-OHP group was increased significantly （P<0.05）. In the Oe+L-OHP group， the expression of anti-apoptotic protein Bcl-2 decreased， the expressions of Bax and Caspase-3 were increased； the expression of autophagosomes was increased； the expressions of Beclin-1 and P62 and the ratio of LC3-Ⅱ/LC3 were all increased （P<0.05）. 【Conclusion】 The RASSF6 gene plays a role in suppressing gastric cancer cell BGC823， which can increase the sensitivity to oxaliplatin chemotherapy by promoting apoptosis and autophagy.

Objective:To study LIM kinase 1 (LIMK1) expressional condition, and its regulatory effects on the proliferation and metastasis of hepatocellular carcinoma cells and tissues.Methods:The online database starBase v3.0 and GEPIA were used to analyze the LIMK1 expression in hepatocellular carcinoma cells and normal liver tissues, and then the relevant survival analysis was performed. LIMK1 expression in hepatocellular carcinoma cell line was analyzed by Western blot. Hep3B and Huh7 cells were transiently transfected after LIMK1 protein expression was down-regulated by small interfering RNA (siRNA). LIMK1 effects on the proliferation of Hep3B and Huh7 cells were observed by MTT assay and colony formation assay. Transwell assay was used to detect the change in metastatic ability of hepatocellular carcinoma cell after the down-regulation of LIMK1 expression. Western blot was used to detect the changes of related indexes in the process of epithelial mesenchymal transition after the down-regulation of LIMK1 expression. Data were analyzed by one-way ANOVA.Results:The expression level of LIMK1 in liver cancer tissues was significantly higher than that of normal liver tissues, and was related with prognosis ( P ?< 0.01). Furthermore, LIMK1 expression in HCC cell lines was significantly higher than that of immortalized liver L02 cells ( P < 0.05). Functional correlated experiment showed that the proliferation and metastatic ability of liver cancer cells were significantly inhibited after LIMK1 expression down-regulation ( P < 0.05). Simultaneously, LIMK1 was also involved in the process of epithelial-mesenchymal transition. Conclusion:LIMK1 was overexpressed in HCC tissues and cells, and may regulate the proliferation and metastasis of HCC cells and participate in epithelial-mesenchymal transition process.

Objective:To study the clinical manifestations, pathologic features, diagnosis and differential diagnosis, treatment and prognosis of lymphoplasmacytic lymphoma/Waldenstr?m′s macroglobulinemia (LPL/WM).Methods:Twenty-seven cases of LPL from January 2016 to December 2020 at Guangdong Provincial People′s Hospital were collected. The clinical data, histomorphology, immunophenotype, MYD88 L265P mutation, treatment and prognosis were analyzed retrospectively.Results:There were 19 males and 8 female patients, with median age of 63 years. The most common initial symptoms were fatigue related to anemia. Bone marrow was involved in all cases, lymphadenopathy was seen in 11 cases and splenomegaly in 10 cases. Monoclonal IgM type protein was detected in 25 cases, meeting the diagnostic criteria of WM. Microscopically, bone marrow and lymph nodes were infiltrated by small lymphocytes, plasmacytoid lymphocytes or plasma cells. The cells expressed pan B-cell markers and showed immunoglobulin light chain restriction. There was no expression of CD5, and low expression of CD23 and CD10; Ki-67 index was usually low. The positive rate of MYD88 L265P mutation was 73.9% (17/23). Most of the patients were treated with rituximab combined with alkylating agents, nucleoside analogues or immunomodulators, and the few patients with relapse or progression were treated with Ibutinib. During the 3-168 months′ follow-up period, recurrence or progression were seen in nine cases. Thrombocytopenia, elevated β2-microglobulin and high-risk group were associated with recurrence or progression of the disease ( P<0.05). The overall survival (OS) and progression-free survival (PFS) of the high-risk patients were significantly lower than those of the low-medium risk patients ( P<0.05). Conclusions:LPL/WM is an exclusive diagnosis; the detection of MYD88 L265P mutation has high diagnostic value, but it is not specific. These cases should be assessed comprehensively for their clinical manifestation, serum IgM protein level and immunophenotype. The overall prognosis of LPL/WM is good, but there are still a small number of high-risk patients with rapid progress, and so the symptomatic patients should be diagnosed accurately and treated in a timely manner.

[Abstract] Objective: To explore the regulatory effect of long non-coding RNA (lncRNA) SNHG5 on invasion and migration of hypoxia-induced hepatocellular carcinoma (HCC) cells. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from HCC patients in the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to June 2018, and human HCC cell lines (HepG2, MHCC-97L, MHCC-97H , Huh7) as well as immortalized human liver LO2 cells were collected for this study. Bioinformatics methods were used to analyze the binding sites between hypoxia-inducible factor 1α (HIF-1α) and SNHG5. pCMVHIF-1α and shRNA-SNHG5 (sh-SNHG5) plasmids were transfected into HCC cells, respectively. qPCR was used to detect the expres‐ sion level of SNHG5 in HCC tissues and hypoxia-induced HCC cells. Western botting was used to detect the expression level of HIF-1α protein in HCC cells, and Transwell chamber method was used to detect the migration and invasion ability of HCC cells after SNHG5 si‐ lence under normoxia and hypoxia condition. Results: Compared with para-cancerous tissues and immortalized human liver LO2 cells, the expression of SNHG5 was significantly up-regulated in HCC tissues and cell lines (all P<0.01). Hypoxia promoted the expression level of SNHG5 in HCC cells, and its mechanism might be related to the combination of hypoxia-activated HIF-1α and SNHG5 promoter to promote its transcription. Hypoxia promoted the invasion and migration ability of HepG2 and MHCC-97L cells (all P< 0.01), but knockdown of SNHG5 significantly inhibited the invasion and migration ability of HepG2 and MHCC-97L cells under hy‐ poxic conditions (all P<0.01). Conclusion: SNHG5 is highly expressed in HCC tissues and cell lines and plays an important role in the invasion and migration of HCC cells induced by hypoxia.

OBJECTIVE: To investigate changes in intestinal flora in patients with primary Sj?gren syndrome (pSS) and explore the relationship between pSS disease activity and intestinal flora structure. METHODS: Fecal samples were collected from 18 female pSS patients, including 9 patients with active disease (group A) and 9 with disease inactivity or low activity (group B), with 10 healthy subjects as the control group. The total bacterial DNA was extracted from the fecal samples for PCR amplification, and Illumina Hiseq 2500 high-throughput sequencing was performed for the v3-v4 region of 16Sr DNA gene to obtain the biological information of the intestinal flora. The intergroup OTU analysis, structural diversity analysis, significant difference analysis and LEFSE analysis were performed with information mining of the literature think tanks. RESULTS: The dilution curves generated based on the OTUshannon index for analysis of sample complexity showed that the measured data were relatively complete and could reflect the diversity of the microorganisms in the subjects. Analysis of the Alpha diversity index showed that the Shannon index differed significantly between group A and group B, and the Simpson index differed significantly between group A and group B and between group A and the control group ( < 0.05). Sequence analysis the 3 groups all consisted mainly of 4 phylum (, , , showed that the intestinal flora in and ) and 4 genera (, , , and ), all showing no significant differences among the 3 groups ( > 0.05) with the exception of genus, which differed significantly among the 3 groups ( < 0.05). The 16S v3-v4 region in the genus , , , , , , , , , , -, and differed significantly among the 3 groups ( < 0.05). The high-dimensional biometrics and genomic characteristics of the intestinal microorganisms differed significantly among the 3 groups ( < 0.05). According to the size of LDA SCORE (effect size), the core flora in group A included the genera , , -, , -, , , , and , as compared with the genera , , , , , -, , - and in the control group. CONCLUSIONS Patients with pSS have significant changes in the diversity of intestinal flora, especially in some specific bacteria in genus and in 16S v3-v4 region of the bacteria. The differences in the core bacteria in the intestinal flora of pSS patients suggest the role of flora structure changes in the pathogenesis of pSS.
Bacteria ; classification ; genetics ; Biodiversity ; DNA, Bacterial ; genetics ; Feces ; microbiology ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S ; genetics ; Sjogren's Syndrome ; microbiology

OBJECTIVE: To investigate changes in intestinal flora in patients with primary Sj?gren syndrome (pSS) and explore the relationship between pSS disease activity and intestinal flora structure. METHODS: Fecal samples were collected from 18 female pSS patients, including 9 patients with active disease (group A) and 9 with disease inactivity or low activity (group B), with 10 healthy subjects as the control group. The total bacterial DNA was extracted from the fecal samples for PCR amplification, and Illumina Hiseq 2500 high-throughput sequencing was performed for the v3-v4 region of 16Sr DNA gene to obtain the biological information of the intestinal flora. The intergroup OTU analysis, structural diversity analysis, significant difference analysis and LEFSE analysis were performed with information mining of the literature think tanks. RESULTS: The dilution curves generated based on the OTUshannon index for analysis of sample complexity showed that the measured data were relatively complete and could reflect the diversity of the microorganisms in the subjects. Analysis of the Alpha diversity index showed that the Shannon index differed significantly between group A and group B, and the Simpson index differed significantly between group A and group B and between group A and the control group ( < 0.05). Sequence analysis the 3 groups all consisted mainly of 4 phylum (, , , showed that the intestinal flora in and ) and 4 genera (, , , and ), all showing no significant differences among the 3 groups ( > 0.05) with the exception of genus, which differed significantly among the 3 groups ( < 0.05). The 16S v3-v4 region in the genus , , , , , , , , , , -, and differed significantly among the 3 groups ( < 0.05). The high-dimensional biometrics and genomic characteristics of the intestinal microorganisms differed significantly among the 3 groups ( < 0.05). According to the size of LDA SCORE (effect size), the core flora in group A included the genera , , -, , -, , , , and , as compared with the genera , , , , , -, , - and in the control group. CONCLUSIONS Patients with pSS have significant changes in the diversity of intestinal flora, especially in some specific bacteria in genus and in 16S v3-v4 region of the bacteria. The differences in the core bacteria in the intestinal flora of pSS patients suggest the role of flora structure changes in the pathogenesis of pSS.
Bacteria ; DNA, Bacterial ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S ; Sjogren's Syndrome