For a long time, many people have believed that traditional Chinese medicines (TCMs) are safe because they derive from natural products. However, this belief has been greatly challenged in recent years especially after some reports on aristolochic acid involved in the genesis of cancer. According to the Chinese pharmacopoeia, many TCMs are known to be toxic, causing damage to the nervous, liver, renal, respiratory, and reproductive system. How to reduce the toxicity of TCMs and how to avoid abuse of TCMs in daily practice is the question? Here, we will give a brief summary and some tips on these issues. First, the accurate differentiation of a specific syndrome is the foundation of an effective and individualized treatment strategy, as well as the key to applying TCMs. Second, through standard processing, proper compatibility, rational decoction, and appropriate dose for TCMs, the harm of TCMs can be effectively avoided. Third, it should be remembered that Chinese herbs cannot be taken continuously as dietary supplements. Finally, Chinese patent medicines should be used with caution. In addition, the dosage of TCMs should not exceed the limit prescribed by the current China Pharmacopoeia, which will ensure the balance of efficacy and toxicity. Taken together, it is necessary to treat the toxicity and safety of TCMs with rationality. The more toxicity we can find, the more safety patients will have.
Transcatheter arterial chemoembolization (TACE) plays an important role in the treatment of unresectable liver cancer. We conducted this meta-analysis to compare the clinical safety and efficacy of conventional TACE (C-TACE) and drug-eluting beads (DEB)-TACE. A search for those procedures was performed using the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis of patients who underwent C-TACE or DEB-TACE was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of 334 studies, 30 were analyzed. The complete response rate, disease control rate, objective response rate, 3-year survival rate, and non-response rate were significantly higher in patients who underwent DEB-TACE than those in patients who underwent C-TACE. The 1-year survival rate, 2-year survival rate, 30-day mortality rate, complete response rate, disease control rate, complete necrosis rate, non-response rate, objective response rate, progressive disease rate, and recurrence did not differ significantly between patients who underwent C-TACE and patients who underwent DEB-TACE. Patients who undergo DEB-TACE might have a higher complete response rate, disease control rate, and 3-year survival rate than patients who undergo C-TACE. Safety did not differ significantly between C-TACE and DEB-TACE.
The earlier assessment of Pueraria tuberosa (PT) has shown anti-diabetic effects through enhancing incretin action and DPP-IV (Dipeptidyl peptidase-IV) inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa tuber (PTY-2) against streptozotocin (STZ) induced islet stress in rats. Diabetes was induced by STZ (65 mg/kg body weight) in charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed after the 10th day of treatment accordingly. STZ treatment led to an increase in expression of Matrix metalloproteinases-9 (MMP-9), Tumour necrosis factor-α (Tnf-α), Hypoxia inducible factor-α (HIF-1α), Vascular endothelial growth factor (VEGF), Interleukin-6 (IL-6), Protein kinase C-ε (PKC-ε), Nuclear factor kappa-light-chain-enhancer of activated B-cells (NFkB), and Caspase-3. Reverse Transcriptase-PCR (RT-PCR), Immunohistochemistry and Western-Blot analysis showed an increase in the expressions of Superoxide Dismutase (SOD) and Nephrin, and a decrease in the expressions of NFkB, PKC-ε, TNF-α, MMP-9, HIF-1α, VEGF, Caspase-3 and IL-6 after 10 days of PTY-2 treatment. The results showed that PTY-2 favorably changed all the expressions via anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory pathways, making itself as a protective agent against STZ induced islet stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.
Postmenopausal osteoporosis (PMO) has become a public health problem worldwide. Hormonal replacement therapy (HRT) is the most popular treatment for PMO at present, but the side effects, including increased risk of endometrial cancer and breast cancer, limit its clinical use. Therefore, finding a new medication with high efficiency and less side-effects is urgently required. Dioscin is the main ingredient of some medicinal plants such as Dioscorea nipponica Makino and Dioscorea zingiberensis Wrigh. It is reported that dioscin has anti-tumoral and anti-atherosclerotic activity as well as an inhibitory effect on hepatic fibrosis. In this study, the effects of dioscin on PMO were examined and the mechanisms were analyzed. The results indicated that the bone mineral density and ultimate load of PMO rats were increased after being treated with dioscin. H&E staining and immunohistochemical staining showed the bone trabeculae formation and bone differentiation of PMO rats were promoted by dioscin. Western blots revealed that dioscin could activate the PI3K/P38/AKT signaling pathway and inhibit the apoptosis signaling pathway in bone tissue cells of PMO rats. In addition, MTT assays showed that MC3T3-E1 cell viability could be improved by dioscin. These results suggest dioscin is a potential therapeutic reagent for osteoporosis and deserves further investigation.
Certain Desulfovibrio sp. (anaerobic sulfate-reducing bacteria) are indigenous to swine cecum and colon, which are also common habitats for parasitic amoebae such as Entamoeba polecki and Entamoeba suis. In this study, we evaluated the growth-promoting effects of D. desulfuricans co-cultured with Escherichia coli (DH5α) and its products [e.g., hydrogen sulfide (H2S) and certain iron-sulfide (FeS) compounds] using Robinson's medium, on the 4 amoeba isolates from swine-Entamoeba polecki subtype (ST)-1, E. polecki ST-3, Entamoeba suis, and Endolimax sp., and, consequently, a continuous culture system for these amoebae was established. However, this novel culture system was required to regulate the excess H2S dissolved in the medium by increasing air space as amoeba isolates thrive only in large air spaces (30-40%). The effects of air space and H2S and FeS compounds on the growth of E. polecki ST-1 (TDP-5) were determined. E. polecki ST-1 (TDP-5) thrived well in culture bottles with an air space of 30-40% (aerobic) (H2S: ~250-400 μmoles/L), but did not grow at all in an air space < 5% (microaerobic) ( H2S:~800 μmoles/L) and in anaerobic vessels (H2S: 20-30 μmoles/L). In both H2S-depleted and FeS compound-depleted conditions, the amoebae sp. could not thrive either. It was hypothesized that an appropriate concentration of H2S and FeS compounds might function as important physiologically active components of electron carriers such as FeS and ferredoxin.
Transplantation with Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) showed great benefits for restoring myocardial function. However, the outcome of WJ-MSCs transplantation was unsuccessful due to multiple factors including oxidative damage. The presence of oxidative stress due to myocardium injury influences fibrous tissue formation, which causes disability of cardiac muscle. Hepatocyte growth factor (HGF), insulin-like growth factor (IGF1), and sonic hedgehog (SHH) are well-known master regulators in anti-fibrosis when secreted by WJ-MSCs. They showed a beneficial role in the recovery of cardiac fibrosis after WJ-MSCs transplantation. This study hypothesizes whether the reduction of the anti-fibrosis property in WJ-MSCs from oxidative damage can be recovered by overexpression of the HGF, IGF1, or SHH gene. Overexpression was attained by transfection of WJ-MSCs with pCMV3-HGF, pCMV3-IGF1, or pCMV3-SHH followed by H2O2 exposure and co-culturing with cardiac fibroblasts. Myofibroblast specific markers comprised of alpha-smooth muscle actin (α-SMA) and collagen type 1 (COL1) were evaluated. The WJ-MSCs treated with H2O2 influenced the expression of myofibroblastic markers, whereas the overexpression of HGF, IGF1 or SHH reduced myofibroblastic formation. These results indicate that the oxidative stress impaired anti-fibrotic property of WJ-MSCs, leads to an increase of myofibroblasts. Overexpression of anti-fibrotic genes restored the endogenous HGF, IGF1, and SHH alleviating improvement of cardiac function.
In-stent restenosis is highly related to the deposition of inflammatory extracellular matrix and the migration of endothelial and vascular smooth muscle cells. The miR-17/TIMP-1/interleukin pathway regulates vascular matrix remodeling and plays an important role in the inflammatory reaction. This study identified miR-17 and its related biomarkers in serum that potentially indicated susceptibility to in-stent restenosis (ISR) after coronary artery stenting. Subjects were 42 patients with single de novo coronary artery lesions who underwent regular coronary angiography one year after percutaneous coronary intervention. The clinical baseline information was recorded. Serum levels of biomarkers (including miR-17, TIMP-1, IL-6, IL-8, IL-2R, TNF-alpha, IL-10, and IL-1beta) were measured with real-time PCR or ELISA. Intergroup comparisons were used to compare patients with or without ISR. Compared to levels in the non-restenosis group, the serum miR-17 level was significantly higher (3.13 ± 0.22 vs. 1.06 ± 0.04, p < 0.01) and the serum TIMP-1 and IL-6 levels were significantly lower in the ISR group (TIMP-1: 0.33 ± 0.04 vs. 1.00 ± 0.05, p < 0.01; IL-6: 1.64 ± 0.18 vs. 3.52 ± 0.11, p < 0.01). Moreover, the levels of TIMP-1 and IL-6 decreased as the level of miR-17 increased. Spearman's correlation analysis indicated that the miR-17 level was inversely correlated with TIMP-1 and IL-6 levels. Findings suggest that an elevated level of miR-17 and decreased levels of TIMP-1 and IL-6 may be associated with the risk of ISR, which is in accordance with vascular matrix remodeling and an inflammatory reaction during the pathologic process of ISR. This study highlighted the potential for miR-17, TIMP-1, and IL-6 to serve as biomarkers for ISR.
Long-term aircraft noise exposure may cast a detrimental effect upon the working memory of military pilots, and the brain structural and functional bases of noise related cognitive impairment remains unclear. In this study, we enrolled 30 fighter jet pilots and 30 matched controls. The working memory performance of the subjects was measured with a neurobehavioral test battery including immediate verbal/visual memory and delayed verbal/visual memory tests. Structural MRI and resting-state functional magnetic resonance imaging (rs-fMRI) were utilized to quantify brain grey matter volumes (GMV), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) differences between the two groups. Furthermore, correlation analyses were performed to find the association between the neural imaging changes with individual neurobehavioral performance. The military pilots showed significantly lower accuracy in delayed verbal and visual memory tests in comparison to the controls, indicating a potential working memory deficit in this population. Structural MRI data and rs-fMRI data showed that the pilots displayed markedly decreased GMVs, ReHo and ALFF signals in the left hippocampus, suggesting neuron dysfunction of the hippocampus. Besides, ReHo and ALFF/fALFF analysis also revealed reduced ReHo in the left amygdala, left thalamus, left superior temporal gyrus and right superior/middle frontal gyrus, indicating disrupted local neural activity under chronic noise exposure. Furthermore, Spearman correlation analysis proved that the GMV and ReHo of left hippocampus were significantly associated with working memory accuracy. This study provided direct evidence of dysfunctional hippocampus serving as the structural and functional bases for neuropsychological impairment under aircraft noise exposure.
In order to investigate the genetic causes of hearing loss in a Chinese proband (in Family A) with enlarged vestibular aqueduct (EVA) and to investigate the genotype of two Chinese probands with SLC26A4 singe-allelic mutation and normal hearing (in Families B and C, respectively), the three probands and their parents were clinically and genetically evaluated. Twenty exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations via amplification with PCR and bidirectional sequencing. As controls, a group of 400 healthy newborns from the same ethnic background underwent SLC26A4 gene screening using the same method. The three probands all harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. The genotypes of mutations in Families A, B, and C are c.1211C>A/c.919-2A>G, c.1729G>A/c.919-2A>G, and c.1286C>A/c.919-2A>G, respectively. The missense mutations c.1211C>A (p.T430Q) in exon 10 and c.1729G>A (p.V577I) in exon 16 are both reported for the first time and were absent in 400 healthy newborns. c.1211C>A has Glutamine (Gln) at amino acid 430 instead of Threonine (Thr), and c.1729G>A has Isoleucine (Ile) at amino acid 577 instead of Valine (Val). c.1286C>A, a mutation previously reported in DVD and HGMD, was associated with Mondini deformity, but a proband with the c.1286C>A mutation in this study was normal. This study has demonstrated that the novel missense mutation c.1211C>A in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is likely to be the cause of deafness in Family A. A novel variant, c.1729G>A, was identified and is likely benign. The pathogenicity of the c.1286C>A mutation warrants more in-depth study. These findings will broaden the spectrum of known SLC26A4 mutations in the Chinese population, providing more information for genetic counseling and diagnosis of hearing loss with EVA.
The use of hepatitis B core antibody (anti-HBc)-positive grafts is one strategy for expanding the donor pool for liver transplantation (LT). The aim of this study was to determine the risk factors associated with hepatitis B virus (HBV) recurrence after living donor LT (LDLT) of anti-HBc-positive grafts. From January 1996 to December 2018, a total of 609 LDLT procedures were performed at our center. A retrospective review was performed for 31 patients (23 males and 8 females; median age = 47 years) who underwent LDLT for HBV-unrelated liver disease from anti-HBc-positive donors. The factors associated with HBV recurrence were evaluated and compared between the HBV recurrence and non-recurrence groups. The median follow-up period after LT was 135 months (range, 6-273 months). Four of 31 patients (12.9%) developed post-LT HBV recurrence. All four cases were HBV-naïve patients (anti-HBc-negative and Hepatitis B surface antibody-negative). The median interval between LDLT and HBV recurrence was 42 months (range, 20-51). The overall actuarial rates of HBV recurrence at 1, 3, 5, 10, and 20 years were 0%, 7.2%, 15.7%, 15.7%, and 15.7%, respectively. Although there were no significant differences between the HBV recurrence and non-recurrence groups, HBV recurrence tended to occur in HBV-naïve recipients (P = 0.093). HBV-naïve status may contribute to HBV recurrence after LDLT for HBV-unrelated liver disease from anti-HBc-positive donors. Careful monitoring for serological HBV markers is needed, particularly in this group.
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is no longer a rarely diagnosed disease, because of the development of medical imaging. With a high incidence of canceration, especially in the main duct type, surgery is strongly recommended. Pancreatoduodenectomy, distal pancreatectomy and central pancreatectomy are applied in those cases. For this potentially malignant disease, function-preserving surgery seems more appropriate. An old female was enrolled in our research, who was diagnosed with IPMN. Diameter of the main pancreatic duct (MPD) was > 5 mm and lesions distributed to the whole pancreas. laparoscopic duodenum and spleen-preserving total pancreatoduodenectomy was carried out, which has not reported previously. We successfully performed laparoscopic duodenum and spleen-preserving total pancreatectomy, without major complications such as severe pancreatic fistula, postoperative bleeding, and delayed ischemia of duodenum and spleen. We consider laparoscopic duodenum and spleen-preserving total pancreatectomy is technically feasible, but a large sample of randomized controlled trials is needed to evaluate its safety, effectiveness and long-term outcome.
Cancer is a major public health issue in China, and effective anticancer drugs remain a huge unmet need. Generic drugs have long been the main products of pharmaceutical companies in China. In this decade, research on and development of innovative drugs has greatly advanced thanks to policy reforms and economic growth. Five innovative anticancer drugs - anlotinib, pyrotinib, fruquintinib, sintilimab, and toripalimab - that were developed by Chinese domestic pharmaceutical companies were approved by the National Medical Products Administration (NMPA) of China in 2018. Several novel anticancer drugs such as avitinib, flumatinib, zanubrutinib, and ensartinib may also receive approval for marketing in China in the near future. There are unprecedented opportunities for development of innovative drugs in China. In the future, innovative drug development in China is poised to shift from "me too" or "me better" drugs to "first-in-class" or "best-in-class" drugs.