Comparison of Quality of Life Between Breast Cancer Patients Treated With and Without Adjunctive Traditional Chinese Medicine in Taiwan.

In Taiwan, breast cancer has the highest incidence among all cancers. Although adjunctive traditional Chinese medicine treatment (TCM) have been used to ameliorate the side effects or discomfort caused by cancer treatments, no study has focused on the assessment of the quality of life of patients undergoing adjunctive TCM treatments. This study compared the quality of life between breast cancer patients treated with and without adjunctive TCM. Questionnaires were collected from 7 hospitals with a Chinese medicine clinic in 2018 to 2019. Breast cancer patients who had cancer stages I, II, or III and also underwent resection surgery were included in the study. They were divided into 2 groups: patients receiving cancer treatments with adjunctive traditional Chinese medicine (TCM group) and those receiving cancer treatments without adjunctive traditional Chinese medicine (non-TCM group). A 1:1 matching was used to obtain the study participants. The EQ-5D questionnaire was used to assess the quality of life. Statistical analysis was performed using the t-test and ANOVA to compare the differences between variables. The conditional multiple regression model was applied to explore the factors associated with quality of life in breast cancer patients. A total of 543 participants were surveyed, and 450 participants were included in the study. The EQ-5D score of the TCM group (81.60 ± 11.67) was significantly higher than that of the non-TCM group (78.80 ± 13.10; P < .05). The results of a conditional multiple regression model showed that the TCM group had a higher (3.45 points) quality of life than non-TCM group (P = .002) after adjusting for other related factors. After stratifying by cancer stage, patients with cancer stages II and III scored 5.58 and 4.35 points higher in the TCM group than did those in the non-TCM group (P < .05). Breast cancer patients undergoing cancer treatment with adjunctive traditional Chinese medicine have a higher quality of life than those treated without adjunctive traditional Chinese medicine.

Analgesia Effect of Verum and Sham Acupuncture Treatments in Primary Dysmenorrhea: A MRI Pilot Study.

Acupuncture is an alternative treatment for primary dysmenorrhea (PDM). However, mechanisms by which acupuncture exerts its analgesic properties are still unclear. This study aimed to explore the cerebral blood flow (CBF) response to verum and sham acupuncture treatments, and further investigate whether pre-treatment CBF is capable of assessing symptom changes after interventions. A total of 11 PDM patients in the verum group and 12 patients in the sham group participated in this study. Pain rating index (PRI), CBF, and gonadal hormone levels were acquired before and after 8-week treatments. Both verum and sham acupuncture treatments exert its analgesic effect on PDM after intervention as PRI reduced (p < 0.05). Blood gonadal levels were not significantly different after acupuncture in both groups (all p > 0.05). In the verum group, intervention-related decreases in CBF were observed in the right dorsal anterior cingulate cortex. In the sham group, regions identified as showing reductions in CBF after acupuncture included the left ventromedial prefrontal cortex, left caudate, and left insula. Patients with higher baseline CBF in the left precuneus and right hippocampus were accompanied with worse treatment response to acupuncture intervention. Mechanisms of verum and sham acupuncture treatments are dissimilar as manifested by different brain responses.

Coprescription Trends in Western Medicine, Chinese Herbal Medicine and Dental Medicine among Older Adults in Taiwan from 1997 to 2013.

BACKGROUND: Coprescription is a potential medical problem for older adults that could induce polypharmacy and subsequent complications. In Taiwan, Chinese herbal medicine (CHM) is popular among the older adults. Investigating the coprescription trends in Western medicine, CHM and dental medicine is important to avoid possible polypharmacy. METHODS: We analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000) in Taiwan. Patients ≥ 60 years old who received coprescription of Western medicine, CHM and drugs for dental care from 1997 to 2013 were included. The odds ratio (OR) and 95% confidence interval (95% CI) were estimated by a logistic regression model for evaluating the correlation between baseline characteristics and coprescription. RESULTS: A total of 266,034 patients were included for the analysis. Most patients receiving coprescriptions lived in the northern Taiwan and with a monthly income lower than 20,000 new Taiwan dollars. The trends in older adults using Western medicine alone or CHM alone decreased over time, but the cohort using dental medicine alone had the opposite result. Decreased trends in coprescription with age were noted. The trends in the proportion of coprescription and the number of days of coprescription increased with the calendar year. Increased trends in the proportion of patients with coprescription were also found, except for the cohort of patients who used both Western medicine and CHM. Patients who were female, and aged 70-79 years were prone to receive coprescription. CONCLUSIONS: Coprescription in older patients is not uncommon in Taiwan. Healthcare providers and policymakers should be aware of the complex coprescription pattern in the older adults.

Acupuncture Treatment Associated with Functional Connectivity Changes in Primary Dysmenorrhea: A Resting State fMRI Study.

Primary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. Acupuncture has been suggested as an effective treatment of PDM that may modulate descending pain modulation systems. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation systems after acupuncture treatment in women with PDM. Thirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention to measure the spontaneous activity in brain. After the 8-week intervention, both verum and sham groups reported decreased menstrual pain. However, the cessation of decreased functional connectivity (FC) between periaqueductal gray matter and the regions associated with affective pain modulation and attention-related pain modulation were found in the verum but not in the sham group after the 8-week intervention. More decreased FC has been found in the region associated with non-specific effects of acupuncture intervention after the early stage of acupuncture intervention. These results indicated that verum acupuncture may intercept the altered FC in descending pain modulation systems in PDM.

Metal-Protein Nanoparticles Facilitate Anti-VSV and H1N1 Viruses Through the Coordinative Actions on Innate Immune Responses and METTL14.

Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6 -methyladenosine (m6 A) modifications during viral infection. Among of them, methyltransferase like-14 enzyme (METTL14) plays an important role in m6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal-protein nanoparticles designated GSTP1-MT3(Fe2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon-beta (IFN-ß) production in vesicular stomatitis virus (VSV)-infected macrophages. Further investigation elucidates that a high dose of IFN-ß can promote the expression of METTL14, which has a well anti-VSV capacity. Moreover, it is found that other negative-sense single-stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative-sense single-stranded RNA viruses infections.

Serum MicroRNA Profiling and Bioinformatics of Patients with Spleen-Deficiency Syndrome.

To investigate serum microRNA (miRNA) profile and bioinformatics of patients with spleen-deficiency syndrome (SDS) and explore pathogenesis of SDS patients from miRNA levels, 10 patients with type 2 diabetes mellitus (T2DM), within which 5 patients were with SDS and the remaining were with blood stasis syndrome (BSS), and 5 healthy volunteers were recruited. Serum miRNA profiles of SDS patients were identified by quantitative PCR array. Target prediction and functional annotation for miRNAs were performed by miRSystem database. The present study identified 11 candidate serum miRNAs for SDS patients, and their targets were significantly enriched in 18 KEGG pathways and 7 GO molecular functions. Those enriched KEGG pathways included (1) metabolisms of carbohydrate, protein, amino acid, and fatty acid, (2) signaling pathways of insulin, ErbB, chemokine, calcium, and type II diabetes mellitus, (3) invasions of bacterium, Escherichia coli, and Shigella (Shigellosis), and (4) endocytosis and phagocytosis. Those enriched GO molecular functions were mainly involved in transcription regulation and regulation of metabolism. Our findings might elucidate the pathogenesis of SDS patients with disorders of substance metabolism and hypoimmunity from miRNA levels, as well as providing some miRNA biomarkers for clinical syndrome differentiation of SDS.

[Effect of Chinese Herbal Extract HNA-1 on the Thymic Output Function in Simian Immunodeficiency Virus Chronically Infected Chinese Rhesus Macaques].

OBJECTIVE: To observe the effect of Chinese herbal extract HuNan A-1 (HNA-1) on the thymic output function in Simian immunodeficiency virus (SIV) chronically infected rhesus macaques. METHODS: Eight Chinese rhesus macaques had been infected by SIVmac239 for 16 to 21 months, and then they were randomly divided into the treatment group and the control group, 4 in each group. Monkeys in the treatment group were administered with HNA-1 by gastrogavage, once daily for 2 successive months, while those in the control group were administered with equal volume of normal saline by gastrogavage, once daily for 2 successive months. The general condition and body weight of monkeys were observed. Plasma viral loads were detected using real-time fluorescent quantitative PCR assay. CD4 percentages and counts, as well as naive CD subsets were detected using flow cytometry. T-cell receptor excision circles (TREC) were detected using real-time fluorescent quantitative PCR assay. The thymus tissue was pathologically observed using routine HE staining. The correlation between lesions of the thymus tissue, CD4 counts, naive CD counts, and TREC were analyzed. RESULTS: There was no statistical difference in body weight, viral loads, absolute CD ratios between the two groups after treatment (P > 0.05). The altered TREC multiple showed an obvious decreasing tendency in the control group, while it showed an increasing tendency in the treatment group (P < 0.05). In both groups, destroyed structures of the thymus tissue could be seen, filled with pink unstructured material. Increased connective tissues, lowered connective cell density, and confused arrangement could also be seen in the two groups, with no obvious difference. TREC contents were positively correlated with naive CD4 counts after removing extremum (r = 0.926, P = 0.001). Naive CD4 counts were positively correlated with CD4 counts (r = 0.961, P = 0.005). CONCLUSIONS: TREC content determination, as a marker of newly thymic emigrants, could be taken as a testing method for evaluating the thymic output function. Besides, HNA-1 treatment increased the thymic output significantly in SIV chronically infected monkeys. Correlation existed among TREC contents, naive CD4 counts, and pathologies of thymus tissues, especially in late infection stage.

Engineering the gut microbiota to treat hyperammonemia.

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

Prescription patterns of Chinese herbal products for patients with uterine fibroid in Taiwan: A nationwide population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Uterine fibroid (myoma) is one of the most common diseases in women. Although there are several studies on the efficacy of Chinese herbs, there is a lack of large-scale survey on the use of traditional Chinese medicine (TCM) for the treatment of uterine fibroid. This study aimed to investigate the utilization of Chinese herbal products for patients with uterine fibroid, prescribed by licensed TCM doctors in Taiwan. MATERIALS AND METHODS: A random sample comprised of one million individuals with newly diagnosed uterine fibroid between 2002 and 2010 from the Taiwanese National Health Insurance Research Database was analyzed. Demographic characteristics, TCM usage, the frequency as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with uterine fibroid, were analyzed. RESULTS: Overall, 35,786 newly diagnosed subjects with uterine fibroid were included. Majority of these patients (87.1%; n=31,161) had visited TCM clinics. Among them, 61.8% of their visits used Chinese herbal remedies. Patients less than 45 years of age tended to use TCM more frequently than elder patients. Gui-Zhi-Fu-Ling-Wan (Cinnamon Twig and Poria Pill) was the most frequently prescribed Chinese herbal formula, while San-Leng (Rhizoma Sparganii) was the most commonly prescribed single herb. CONCLUSIONS: Our study identified the characteristics and prescription patterns of TCM for patients with uterine fibroid in Taiwan. Further basic mechanistic studies and clinical trials are needed to confirm the therapeutic effects and mechanisms.

Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment.

Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract. The abundance of fungi and bacteria was measured using quantitative PCR, and the proportional composition of the communities quantified using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria dropped in abundance >3 orders of magnitude, so that the predominant 16S sequences detected became transients derived from food. Upon cessation of treatment, bacterial communities mostly returned to their previous numbers and types after 8 weeks, though communities remained detectably different from untreated controls. Fungal communities varied substantially over time, even in the untreated controls. Separate cages within the same treatment group showed radical differences, but mice within a cage generally behaved similarly. Fungi increased ∼40-fold in abundance upon antibiotic treatment but declined back to their original abundance after cessation of treatment. At the last time point, Candida remained more abundant than prior to treatment. These data show that 1) gut fungal populations change radically during normal mouse husbandry, 2) fungi grow out in the gut upon suppression of bacterial communities with antibiotics, and 3) perturbations due to antibiotics persist long term in both the fungal and bacterial microbiota.

Baicalin induces apoptosis in leukemia HL-60/ADR cells via possible down-regulation of the PI3K/Akt signaling pathway.

BACKGROUND: The effect and possible mechanism of traditional Chinese medicine, baicalin, on the PI3K/ Akt signaling pathway in drug-resistant human myeloid leukemia HL-60/ADR cells have been investigated in this current study. METHODS: HL-60/ADR cells were treated by 20, 40, 80 µmol/L baicalin followed by cell cycle analysis at 24h. The mRNA expression level of the apoptosis related gene, Bcl-2 and bad, were measured by RT-PCR on cells treated with 80 µmol/L baicalin at 12, 24 and 48hr. Western blot was performed to detect the changes in the expression of the proteins related to HL-60/ADR cell apoptosis and the signaling pathway before and after baicalin treatment, including Bcl-2, PARP, Bad, Caspase 3, Akt, p-Akt, NF-κB, p-NF-κB, mTOR and p-mTOR. RESULTS: Sub-G1 peak of HL-60/ADR cells appeared 24 h after 20 µmol/L baicalin treatment, and the ratio increased as baicalin concentration increased. Cell cycle analysis showed 44.9% G0/G1 phase cells 24 h after baicalin treatment compared to 39.6% in the control group. Cells treated with 80 µmol/L baicalin displayed a trend in decreasing of Bcl-2 mRNA expression over time. Expression level of the Bcl-2 and PARP proteins decreased significantly while that of the PARP, Caspase-3, and Bad proteins gradually increased. No significant difference in Akt expression was observed between treated and the control groups. However, the expression levels of p-Akt, NF-κB, p-NF-κB, mTOR and p-mTOR decreased significantly in a time-dependent manner. CONCLUSIONS: We conclude that baicalin may induce HL-60/ADR cell apoptosis through the PI3K/AKT signaling pathway.

Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance.

Rheumatoid arthritis is characterized by the imbalance of T cells, which leads to increased pro-inflammatory and reduced anti-inflammatory cytokines. Modulating the balance among T cells is crucial for the treatment of RA. Kirenol is a major diterpenoid components of Herba Siegesbeckiae, which has been applied for arthritic therapy for centuries. Since prior research showed Kirenol exhibited anti-inflammatory effect in rats, in this study we have evaluated the effect and mechanism of bioactive Kirenol in a rat model of collagen-induced arthritis (CIA) on modulation of T cells. After immunization with bovine type II collagen (CII), Wistar rats were orally administered saline (CIA group), 2 mg/kg Kirenol or 2 mg/kg prednisolone daily for 30 days. The severity of arthritis was clinically and histologically assessed. The numbers of CD4⁺CD25⁺Foxp3⁺ T regulatory cells (Tregs) and IFNγ⁺CD4⁺ and IL4⁺CD4⁺ T cells were determined by flow cytometry, the mRNA expression level of Foxp3 was quantified by RT-PCR, cytokine levels were measured by ELISA and CII-induced cell proliferation was quantified in vitro. Kirenol significantly delayed the occurrence and reduced the disease severity of CIA. Histological analysis confirmed Kirenol suppressed joint inflammation and inhibited cartilage and bone destruction, compared to the CIA group. Kirenol also upregulated the mRNA expression of Foxp3, increased the numbers of CD4⁺CD25⁺Foxp3⁺ and IL4⁺CD4⁺ T cells, and reduced the number of IFNγ⁺CD4⁺ T cells. Kirenol reduced the levels of TNF-α, IL-17A and IL-6 in synovial fluid and TNF-α, IL-17A and IFN-γ in serum, and increased the serum levels of IL-4, IL-10 and TGF-ß1. In addition, Kirenol inhibited the ability of CII to induce splenocyte, PBMC and lymph node cell proliferation in vitro, compared to cells from CIA rats. In conclusion, these results suggest that Kirenol may be a potential immunosuppressant for the treatment for rheumatoid arthritis.

RSC96 Schwann Cell Proliferation and Survival Induced by Dilong through PI3K/Akt Signaling Mediated by IGF-I.

Schwann cell proliferation is critical for the regeneration of injured nerves. Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue survival remains unclear. The aim of the present study was to investigate the molecular mechanisms by which Dilong promote neuron regeneration. Our results show that treatment with extract of Dilong induces the phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle analysis showed that G(1) transits into the S phase in 12-16 h, and S transits into the G(2) phase 20 h after exposure to earthworm extract. Strong expression of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K protein expression levels, resulting in Bcl(2) survival factor reduction and a marked blockage of G(1) to S transition in proliferating cells. These results demonstrate that Dilong promotes the proliferation and survival of RSC96 cells via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein.

[Effect of emodin on induction of apoptosis in jurkat cells and its possible mechanisms].

The aim of study was to investigate the effect of a traditional Chinese medicine, emodin, on proliferation and apoptosis in T lymphocytic leukemic cell line Jurkat and its mechanisms. Cell proliferation inhibition was detected by MTT assay. Cell apoptosis was measured by DNA ladder and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The expressions of related proteins and caspase family members were determined by Western blot. The results showed that emodin inhibited proliferation in Jurkat cells, with an IC50 about 20 micromol/L and induced cell apoptosis in both time-and dose-dependent manners. The expressions of proliferation-related protein C-MYC, hTERT and apoptosis-related protein BCL-2 were down-regulated in a time dependent manner after the treatment with emodin. The expressions of procaspase-3, -8 and -9 all decreased while activated caspase-3 and PARP expressions were up-regulated. It is concluded that emodin can remarkably inhibit cell proliferation and induce apoptosis in Jurkat cells. The down-regulation of proliferation-related proteins C-MYC, hTERT and apoptosis-related protein BCL-2 expressions and activation of caspase cascade may be involved in the process of apoptosis.

[Effects of zhiling capsule on the proliferation inhibition and apoptosis induction in human small cell lung cancer cell line NCI-H446].

OBJECTIVE: To investigate the effects of Zhiling Capsule (ZLC) on the proliferation inhibition and apoptosis induction in human small cell lung cancer cell line NCI-H446. METHODS: According to the different components of ZLC, NCI-H446 cells were treated with traditional Chinese medicine, Western medicine and ZLC compound groups. The rates of cell viability and colony formation were observed by MTT assay and colony formation assay respectively. Cell cycle assay, Bcl-2 protein expression, chondrial transmembrane potential and Caspase-3 activity were detected by flow cytometer. Apoptotic cells were detected by DNA fragmentation assay, Annexin-V FITC staining and TUNEL labeling methods. RESULTS: After NCI-H446 cells were treated with various concentrations of drug groups, cell growth was significantly inhibited in a dose dependent manner. Cell colony formation was obviously lowered in the same way. The levels of chondrial transmembrane potential and Bcl-2 protein expression were decreased, while the levels of Caspase-3 activity were increased after the treatment. Typical DNA ladder were seen from gel electrophoresis, and apparent apoptotic peaks were observed by flow cytometer. Apoptosis occured in the early and late stage was identified by Annexin-V FITC staining and TUNEL labeling methods respectively. The ZLC compound group has stronger apoptosis induction than the other groups. CONCLUSION: ZLC could efficiently inhibit growth and induce apoptosis in NCI-H446 cells, which may be related with the down-regulation of chondrial transmembrane potential and Bcl-2 protein expression and the up-regulation of Caspase-3 activity.

[Inhibiting cerebral glioma growth with continuous low-dose chemotherapy and cyclooxygenase-2 inhibitor in nude mice].

OBJECTIVE: To observe the changes in glioma growth characteristic and apoptosis of tumor cells after single handed continuous low-dose chemotherapy, cyclooxygenase-2 inhibitor treatment alone and the combination of the two treatments. METHODS: The U251MG cells in exponential phase of growth were made into 10(7)/mL cell suspension in free-serum 1640 and stored in 37 degrees C incubator. The survival rate of cells was above 95%. The U251MG cells were implanted into the right parietooccipital lobe of the 4-week old nude mouse with a 5 micro liter micro amount sample injector. The number of injected U251MG cells was 5 x 10(4) for a mouse. Twenty days after the model making, the nude mice were treated with elemene and indometacin respectively and the combination of them, twice a week. The mice were divided into four groups. Group I was treated with indometacin alone, group II elemene alone, group III low-dose elemene plus indometacin, Group IV was used as controls, including tumor control and blank control. The animals were killed on the 40th and 50th day after implantation by breaking cervical vertebra. The fixed brain was made into 3 microm slices by paraffin section. The slices were carried out with HE staining and immunohistochemical staining of glial fibrillary acidic protein(GFAP), cell proliferation-associated antigen(Ki-67), cyclooxygenase-2(COX-2), CD34, programmed cell death 5(PDCD5) and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling(TUNEL). RESULTS: The proliferation of glioma cells was predominant in the tumor control mouse brain. Several immature blood vessels were observed in the tumor implanted for 40 days. The white matter was infiltrated by bulk glioma cells along with capillary vessel clusters in the mouse brain implanted for 50 days. In groups with combination treatment of the two drugs, 40 days after the implantation, several apoptosis cells and glioma cells were observed in tumor where the positive signal for GFAP was showed; and 50 days after the implantation, lots of apoptosis cells were observed in tumor cell implantation area where the negative signal for GFAP and positive signal for PDCD5 was showed. The volume of tumor was (29.8+/-39.1) mm(3) 40 days after the implantation, and (78.4+/-125.9) mm(3) 50 days after the implantation. There was no statistically significant difference in tumor volume among groups(P=0.11). CONCLUSION: The combination of two treatments could merely prolong the survival time of the nude mouse model, without the effect of eliminating the tumor completely.