Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.
Adult ; Animals ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Medicine, Tibetan Traditional ; Mice ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult

α-HgS is the main component of traditional Chinese medicine cinnabar, while β-HgS is the main component of Tibetan medicine Zuotai. However, there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar, Zuotai, α-HgS and β-HgS. In this study, the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions. To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms, mice were orally administered with clinical equivalent doses cinnabar and Zuotai. Meanwhile, a group of mice was given α-HgS and β-HgS with the equivalent mercury with cinnabar, while another group was given β-HgS and HgCl2 with the equivalent mercury with Zuotai. The mercury absorption and bioaccumulation capacities of different medicines in mice and their mercury bioaccumulation in different tissues and organs were compared. The experimental results showed a high mercury dissolutions of Zuotai in artificial gastrointestinal fluid, which was followed by β-HgS, cinnabar and α-HgS. As for the mercury absorption and bioaccumulation in mice, HgCl2 was the highest, β-HgS was the next, and a-HgS was slightly higher than cinnabar. The organs with the mercury bioaccumulation from high to low were kidney, liver and brain. This study is close to clinical practices and can provide reference for the clinical safe medication as well as a study model for the safety evaluation on heavy metal-containing medicines by observing the mercury dissolution, absorption, distribution and accumulation of mercury-containing medicines cinnabar and zuotai.
Animals ; Brain ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Gastrointestinal Tract ; metabolism ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Mercury ; chemistry ; pharmacokinetics ; Mercury Compounds ; chemistry ; pharmacokinetics ; Mice ; Solubility

The expression of histone lysine-specific demethylase 1 (LSD1) in colorectal cancer cells is increased, and LSD1 is closely related to its occurrence, development, proliferation, invasion and metastasis. LSD1 is a demethylase whose function depends on flavin adenine dinucleoside. It can specifically catalyze the demethylation reaction of histone lysine, and regulate the expression of target genes by reaction of demethyl and dimethyl (H3K4me, H3K4me2, H3K9me, and H3K9me2) at the 4th and 9th positions of lysine H3. Targeted inhibition of LSD1 has been proved to be able to exert significant anti-tumor effect, but since the tumors involve multiple centers and factors, later studies have found that single inhibition of LSD1 cannot completely and effectively kill tumor cells. Moreover, the specificity of the LSD1 catalytic substrate depends to a large extent on the synergistic factors that bind to it and form complexes. The double-target inhibitors based on LSD1 shows more remarkable effect in tumor inhibition. Therefore, finding the combined synergistic factors of LSD1 may provide the basis for the research of multi-target inhibitors.

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.
Adolescent ; Adult ; Breast Neoplasms ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Phyllodes Tumor ; Prognosis ; Retrospective Studies ; Risk Factors

HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang.
Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; HIV Infections ; diagnosis ; etiology ; transmission ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Young Adult

In recent years, enterovirus infection has become a frequent epidemic and developed into an important public health problem. For example, hand-foot-mouth disease has become a common infection among children in China. Hand-foot-mouth disease (HFMD) has been spreading globally since 1997, especially in the Asia-Pacific region. Enterovirus 71 (EV71) is one of the main pathogens causing HFMD. And now there is no drug available to treat EV71 infection. This review summarizes the research progress of anti-enterovirus-71 drugs from the perspective of medicinal chemistry.

The common development of multi-disciplinary intersection is a hot spot in the research of acupuncture- moxibustion translational medicine. This article analyzes the current situation and reasons for slow development of acupuncture-moxibustion translational medicine, takes acupuncture-moxibustion for depressive disorder as an example, takes acupuncture and moxibustion literature, clinical evidence-based, biological mechanism and medical equipment research and development as the main line, expounds potential strategies to promote the development of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation, and discusses the future research direction of acupuncture-moxibustion translational medicine.
Translational Science, Biomedical

OBJECTIVE: To explore the effect of abnormal miRNA expression on the proliferation of pediatric acute lymphoblastic leukemia (ALL) cells and its related mechanism. METHODS: 15 children with ALL and 15 healthy subjects were collected from the Second Affiliated Hospital of Hainan Medical University from July 2018 to March 2021. MiRNA sequencing was performed on their bone marrow cells, and validated using qRT-PCR. MiR-1294 and miR-1294-inhibitory molecule (miR-1294-inhibitor) were transfected into Nalm-6 cells, and the proliferation of Nalm-6 cells was detected by CCK-8 and colony formation assays. Western blot and ELISA were used to detect apoptosis of Nalm-6 cells. Biological prediction of miR-1294 was performed to find the target gene, which was verified by luciferase reporter assay. Si-SOX15 was transfected into Nalm-6 cells, Western blot was used to detect the expression of Wnt signaling pathway-related proteins and to verify the effect of si-SOX15 on the proliferation and apoptosis of Nalm-6 cells. RESULTS: Compared with healthy subjects, 22 miRNAs were significantly upregulated in bone marrow cells of ALL patients, of which miR-1294 was the most significantly upregulated. In addition, the expression level of SOX15 gene was significantly reduced in bone marrow cells of ALL patients. Compared with the NC group, the miR-1294 group showed increased protein expression levels of Wnt3a and β-catenin, faster cell proliferation, and more colony-forming units, while caspase-3 protein expression level and cell apoptosis were reduced. Compared with the NC group, the miR-1294-inhibitor group showed reduced protein expression levels of Wnt3a and β-catenin, slower cell proliferation, and fewer colony-forming units, while caspase-3 protein expression level was increased and apoptosis rate was elevated. miR-1294 had a complementary base-pair with the 3'UTR region of SOX15 , and miR-1294 directly targeted SOX15 . The expression of miR-1294 was negatively correlated with SOX15 in ALL cells. Compared with the si-NC group, the si-SOX15 group showed increased protein expression levels of Wnt3a and β-catenin, accelerated cell proliferation, and decreased caspase-3 protein expression level and cell apoptosis rate. CONCLUSION MiR-1294 can target and inhibit SOX15 expression, thus activating the Wnt/β-Catenin signaling pathway to promote the proliferation of ALL cells, inhibit cell apoptosis, and ultimately affect the disease progression.
Humans ; Child ; beta Catenin/genetics* ; Wnt Signaling Pathway ; Caspase 3/metabolism* ; Cell Line, Tumor ; MicroRNAs/genetics* ; Cell Proliferation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Apoptosis ; SOX Transcription Factors/metabolism*

OBJECTIVETo investigate Chinese medical features of acquired immunodeficiency syndrome (AIDS) patients with pulmonary infection.

METHODSUsing cluster analysis method, Chinese medical syndromes of 196 AIDS patients with pulmonary infection were analyzed. The distribution features of each syndrome type were analyzed according to the severity and CD4+ numerical analysis.

RESULTSBasic Chinese medical syndrome types could be summed up as three kinds: exterior invasion of wind heat and phlegm heat obstructing Fei syndrome (61 cases, 31.1%), Fei-Pi deficiency and Fei stagnation of phlegm syndrome (64 cases, 32.7%), Fei-Shen deficiency and yin deficiency induced inner heat syndrome (71 cases, 36.2%). There was statistical difference in the severity degree and the distribution of CD4 among the three syndrome types (P < 0.05).

CONCLUSIONSAIDS patients with pulmonary infection involve Fei, Shen, and Pi. The pathogenic factors were related to "wind", "heat", "phlegm", and "xu". The Chinese medical syndrome distribution was closely correlated with patients' immunity.

Acquired Immunodeficiency Syndrome ; complications ; diagnosis ; epidemiology ; Adolescent ; Adult ; Aged ; Cluster Analysis ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Respiratory Tract Infections ; diagnosis ; epidemiology ; etiology ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis ; Young Adult

Humans ; Hearing Loss/etiology* ; Lupus Erythematosus, Systemic/complications* ; Prognosis