As the reform of Chinese medical and health undertakings has advanced (since 2015), the admission, pricing and payment policies regarding the new health technologies of China have undergone significant changes, and health technology assessment (HTA) has gradually become one of the current reform and research hotspots in China. Based on the perspective of HTA driving factors and the development mode, this paper proposes a two-stage mode of HTA development in China, namely, the mode driven by the management of new heath technology admission and another one driven by new health technology pricing and medical insurance payment. In addition, the paper also proposes the challenges that HTA faces in China under the current mode, including the development system, process standard, data mechanism, and policy application. Besides, recommendations are provided for the further development of HTA construction in China, including strengthening the development system of regional HTA centers, formulating HTA process guidance, building a database, improving evaluation quality and intensifying policy integration.
Acute upper respiratory tract infections (AURTIs) are common and self-limited in people with normal immunity but sometimes lead to poor clinical outcomes under specific conditions such as pregnancy if not treated appropriately. Chinese herbal medicines (CHM), which are widely used to treat AURTIs, have proven to be effective in preclinical and clinical studies. This review focuses on the bioactivities of typical CHM and the adverse reactions they cause, and especially issues with reproductive safety when treating AURTIs. The main mechanisms for clinical efficacy may include anti-viral, anti-bacterial, anti-inflammatory, antipyretic, and immunomodulatory action as indicated by preclinical evidence. Most clinical trials indicate that CHM shortens the natural course of AURTIs and that it relieves related symptoms such as a fever, headaches, coughing, myalgia, a cold, sore throat, and a nasal obstruction. However, some CHM have a range of adverse effects and potentially affect reproduction from endocrinal secretion to embryo development while others do not. Therefore, clinical adverse reactions and preclinical studies on the toxicity of CHM are discussed. More reliable evidence is required to conclude that CHM are efficacious and safe for pregnant women with AURTIs. This review should help to promote advances in the research on and development of CHM as alternative treatments for AURTIs and offer insight into strategies to manage the safety of CHM during clinical use.
Single nucleotide polymorphisms (SNP) influence the outcome of antiviral therapy in chronic hepatitis B patients. Interferon β promoter stimulator 1 polymorphisms (IPS-1) regulate interferon (IFN) mediated viral clearance in hepatitis B virus (HBV) infection. In our study, HepG2 and HepG2.2.15 were transfected with different SNP genotype expression vectors of IPS-1 (wild-type, rs17857295, rs7262903 and rs7269320). The production of IPS-1 and IFN were evaluated in these transfected cells. IPS-1 in the HepG2.2.15 cells transfected with rs17857295 or rs7262903 was 37% or 31% lower than that with wild-type transfection (p < 0.001). IFN-β in rs17857295 or rs7262903 transfected HepG2.2.15 cells was 5.4 or 3.7 fold higher than that of wild-type transfection (p < 0.0001). IPS-1 in rs7269320 SNP transfected HepG2.2.15 cells was 40% lower than that of wild-type transfection (p < 0.0001); no significantly different IFN-β was observed between rs7269320 SNP and wild-type transfections. IFN-β expression was > 2 fold higher in rs17857295 transfected HepG2.2.15 cells than HepG2 cells (p < 0.001). The data suggests that host HBV viral clearance is stronger in IPS-1 rs17857295 or rs7262903 SNP genotype patients than wild-type patients. Relatively weak inducible IFN-β production in HBV infected patients with IPS-1 rs7269320 SNP or wild-type may contribute to chronic virus infection.
We construct and validate a non-invasive clinical scoring model to predict mortality in HIV/TB patients at end stage of AIDS in China. There were 1,007 HIV/TB patients admitted to Beijing Ditan Hospital from August 2009 to January 2018 included in this study, who were randomly assigned to form derivation cohort and validation cohort. A clinical scoring model was developed based on predictors associated with mortality identified with Cox proportional hazard models. The discrimination and accuracy of model were further validated using the area under the ROC curves. The derivation and validation cohort consisted of 807 and 200 patients in 8:2 ratio, respectively. In derivation cohort, anemia (HGB < 90g/L), tuberculous meningitis, severe pneumonia, hypoalbuminemia, unexplained infections or space-occupying lesions, and malignancies remained independent risk factors of mortality in HIV/TB co-infected patients, and included in this clinical scoring model. The model indicated good discrimination, including AUC = 0.858 (95% CI: 0.782-0.943) in the derivation cohort, and AUC = 0.867 (95% CI: 0.832-0.902) in validation cohort, respectively. The predicted scores were categorized into two groups to predict the mortality: low-risk (0-2 points with mortality with 3.6-9.1%) and high-risk (4-16 points with mortality with 26.42-74.62%), in which 54.55% and 74.62% of patients with score of 5 to 11 and 12-16 were died among high-risk group. Kaplan-Meier curve indicated a significant difference in the cumulative mortality in the two groups by log-rank test (p < 0.001). A clinical scoring model to assess the prognosis in HIV/TB patients at end stage of AIDS was constructed based on simple laboratory and clinical features available at admission, which may be an easy-to-use tool for physicians to evaluate the prognosis and treatment outcome in HIV/TB co-infected patients. The model was also applicable for predicting the death of end-stage HIV/TB patients within a 12 months period after discharge.
Streptococcus pyogenes causes several infectious diseases such as tonsillitis, cellulitis, and streptococcal toxic shock syndrome. As antibiotics are used for the general treatment of S. pyogenes infection, cases of treatment failure due to drug-resistant bacteria have increased. Lonicera caerulea var. emphyllocalyx (LCE) has been used as a folk medicine in northern Japan (Hokkaido). In this study, we investigated the antibacterial effect of methanol extracts of the fruit, stem, and leaf of LCE (LCEEs) against S. pyogenes using disk diffusion assay. As LCEE (fruit) had the strongest antibacterial activity among the three LCEEs, we focused on functional analysis of antibacterial effects of LCEE (fruit). LCEE (fruit) suppressed the growth of S. pyogenes in a dose-dependent manner. Morphological analysis by transmission electron microscopy demonstrated that LCEE (fruit) damaged the shape of S. pyogenes. Microplate and confocal laser microscopy analysis showed that biofilm formation was also suppressed by LCEE (fruit) in a dose-dependent manner. To further evaluate the surface structure of these biofilms, we performed hydrophobic analysis, which demonstrated that LCEE (fruit) reduced the hydrophobicity of the bacterial surface structure. Our data demonstrated that LCEE (fruit) had anti-bacterial and anti-biofilm effects on S. pyogenes in vitro, suggesting that the direct anti-bacterial effects of the LCEE (fruit) may be useful for treatment of local S. pyogenes infection.
The objective of this study is to evaluate the predictive value of sperm DNA fragmentation Index (DFI) in unexplained recurrent spontaneous abortion (RSA) and to investigate its correlation with conventional sperm parameters. Besides, we aimed to reveal the necessity of establishing a DFI clinical threshold of each laboratory for the prognostic diagnosis of RSA and establish our own DFI threshold. Semen samples were collected from male partners of RSA patients (n = 139) and healthy recent fathers (control, n = 200). DFI was tested using SCSA and conventional semen analysis was performed using an automatic semen analyzer. The DFI value and distribution were compared between the two groups using corresponding statistical software. The diagnostic threshold value was established by ROC curve. The correlation between DFI and the conventional semen parameters of the 139 cases was further analyzed using Student's t test and Mann-Whitney U test. Our result showed that DFI was significantly higher in RSA patients compared with normal donor controls. We established our own DFI threshold at 13.59%. There was only a weak partial correlation between DFI values and conventional sperm analysis parameters. Our present study suggested that DFI might be used as a valuable predictor for RSA independent of conventional sperm parameters. Additionally, we recommend that each laboratory should establish its own clinical DFI threshold for more precise prediction of RSA and we recommend that sperm DNA fragmentation test should be included in complete sperm quality assessment in addition to conventional semen analysis for RSA male partners.
Plant sterols (phytosterols) have been widely accepted as a natural anti-cancer agent in multiple malignant tumors. This study was designed to investigate the functions of daucosterol in prostate cancer progression and its possible molecular mechanisms. Our results showed that daucosterol inhibited cell proliferation and induced cell cycle arrest. Moreover, daucosterol treatment obviously promoted apoptosis and autophagy. An autophagy inhibitor, 3-methyladenine (3-MA) was proved to counteract daucosterol-triggered autophagy, growth inhibition, and apoptosis, indicating that daucosterol-induced apoptotic response was dependent on autophagy. Additionally, treatment with daucosterol resulted in increased phosphorylation of c-Jun N-terminal kinase (JNK). Furthermore, pre-treatment with a JNK-specific inhibitor SP600125 abated daucosterol-elicited autophagy and apoptotic cell death. Taken together, our findings demonstrated that daucosterol blocked prostate cancer growth at least partly through inducing autophagic-dependent apoptosis via activating JNK signaling, providing a promising candidate for the development of antitumor drugs in prostate cancer treatment.
The study aims to analyze oxidative stress levels in circulation of some reactive molecules and products of biomolecular modification in type 2 diabetes mellitus (T2DM) with diabetes-specific vascular complications in order to determine their predictive value. Also, the alterations of their serum concentration with reference to disease characteristics were assessed. Reactive oxygen species (ROS), nitric oxide radicals (•NO), malondialdehyde (MDA), protein carbonyl (CO) and 8-hydroxydeoxyguanosin (8-OHdG) in serum were measured in 93 patients with T2DM with vascular complications, 94 control subjects and 16 diabetic patients who had no evidence of vascular disease. T2DM patients with clinically manifest vascular disease exhibit significantly elevated concentrations of all pro-oxidants in comparison to healthy subjects, with the highest degree of increase of •NO radicals. The levels of carbonylated proteins, ROS and 8-OHdG were significantly increased in insufficiently compensated diabetes as compared to good glycemic control state. Also, serum MDA, protein CO and 8-OHdG showed an association with glycemic control parameters. MDA, ROS and 8-OHdG correlated mostly with microvascular complications. Significant area under the curve (AUC) from plotted receiver operating characteristic (ROC) curves were obtained for all studied biomarkers, as for nitric oxide it was substantially bigger compared to those for the other pro-oxidants. Correspondingly, positive and negative predictive values related to the disease were in favor of the •NO radicals. The cutoff values of oxidative biomarkers may serve as an indicator of clinical reference for detecting T2DM with associated vascular complications, as nitric oxide radicals were the most reliable indicator.
There is little information concerning the prognostic significance of combined albumin- bilirubin (ALBI) grade and aspartate aminotransferase-to-platelet count ratio index (APRI) in hepatocellular carcinoma (HCC). Therefore, we performed this study to assess the prognostic utility of combining ALBI and APRI (ALBI-APRI score) for predicting the prognosis of patients with HCC within Milan criteria after liver resection. Two hundred thirty-nine patients were involved in this study. Patients with a high APRI score were allocated a score of 1, whereas patients with a low APRI score were allocated a score of 0. The ALBI-APRI score is the summation of APRI score and ALBI grade. The area under the receiver operating characteristic curve (AUC) was used to estimate the predictive accuracy of different models. During the study period, 132 patients experienced recurrence, and 52 patients died. Multivariate analysis revealed the ALBI-APRI score (HR = 1.753, 95% CI = 1.293-2.377, p < 0.001), presence of microvascular invasion (MVI, HR = 2.693, 95%CI = 1.832-3.960, p < 0.001) and multiple tumors (HR = 1.973, 95% CI = 1.300-2.995, p = 0.001) were all associated with recurrence. In addition, blood transfusion (HR = 3.113, 95% CI = 1.677-5.778, p < 0.001), high preoperative alpha-fetoprotein (AFP, HR = 2.272, 95% CI = 1.298-3.976, p = 0.004), ALBI-APRI score (HR = 2.046, 95% CI = 1.237-3.382, p = 0.005) and presence of MVI (HR = 4.524, 95% CI = 2.514-8.140, p < 0.001) were correlated with postoperative mortality. The AUCs of ALBI-APRI score were significantly higher than either ALBI or APRI alone for predicting both postoperative recurrence and mortality. ALBI-APRI score may be a predictor for the prognosis of patients with HCC within Milan criteria following liver resection. A more well-designed and large-scale study are warranted to prove our findings.
Standard treatment options for brain metastases (BM) from colorectal cancer (CRC) are controversial. The purpose of this study was to evaluate the efficacy of multidisciplinary treatment modalities and provide optimal therapeutic strategies for selected patients with different clinical characteristics. All eligible patients diagnosed with BM from CRC during the past two decades (1997-2016) were identified in our center. Clinical characteristics, treatment modalities and relative survival were retrospectively analyzed. Median overall survival after the identification of BM was 6 months. The 1- and 2- year survival rates were 29.40% and 5.70%, respectively. On multivariate analysis, the number of BMs, Karnofsky performance score and the treatment modalities were found to be independent prognostic factors (the p-value was 0.006, 0.001 and < 0.001, respectively). In conclusion, multidisciplinary treatment is supported to be the optimal treatment for patients with BM from CRC. For patients with single brain metastases and KPS > 70, neurosurgery combined with chemotherapy could provide an additional survival benefit. For patients with multiple brain metastases or KPS ≤ 70, radiotherapy plus chemotherapy may be appropriate.
Administration of the selective arginine vasopressin V2 receptor antagonist tolvaptan to cirrhotic patients is controversial. There are no reports of tolvaptan use for patients with far-advanced end-stage liver disease (ESLD) and refractory ascites awaiting liver transplantation. Between 2013 and 2016, 64 patients awaiting adult-to-adult living donor liver transplantation (LDLT) were screened for enrollment. Patients with refractory ascites and on dual conventional diuretics (≥ 50 mg/day of spironolactone and ≥ 20 mg/day of a loop diuretic) were enrolled and assigned to the tolvaptan (TOL) group (n = 10), and low-dose tolvaptan, 3.75 mg/day, was started. The remaining patients who had no or little ascites on conventional diuretic therapy (CDT) were assigned to the CDT group (n = 23). The median model for end-stage liver disease and Child-Pugh scores were 16 (range 7-41) and 10 (7-15), respectively. The median dose of spironolactone in the TOL group was 88 mg (range 50-200) vs. 50 (0-100) in the CDT group (p < 0.01). The median dose of loop diuretics in the TOL group was 70 mg (20-120) vs. 20 (0-80) in the CDT group (p = 0.03). No significant liver damage was detected during tolvaptan therapy. Tolvaptan demonstrated favorable effects in 60% (6/10) of the patients, decreasing the body weight by at least 1.5 kg during the 7 day treatment. These findings suggest that low-dose of tolvaptan may be safe for patients having far-advanced ESLD patients with apparent and refractory ascites taking dual conventional diuretics for a short period before LDLT.
Histone deacetylase is an important member of epigenetics and a well validated target for anti-cancer drug discovery. In this study, we designed and synthesized a series of twenty-one novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward histone deacetylases at the concentration of 1 μM. Among them, the inhibition rates of two compounds MH1-18 and MH1-21 exceeded 90%. Furthermore, these two compounds selectively inhibited the activity of histone deacetylase 6 with low IC50 values. The high potency of them toward histone deacetylase 6 was rationalized by molecular docking studies. We found that MH1-18 and MH1-21 moderately inhibited the proliferation of four human cancer cell lines SGC-7901, NCI-H226, MCF-7, and HL-60. However, MH1-21 showed potent efficacy in suppressing the migration of MCF-7 cells. Results obtained in the current study shed light on designing potent HDAC6 inhibitors as anti-cancer agents.
Circular RNA (circRNA) is a class of endogenous non-coding RNAs that are closely related to the pathogenesis of many human diseases, particularly cancer. However, the characterization of circRNAs in high-grade serous ovarian cancer (HGSOC) remains unknown. This study aimed to investigate the expression profile of circRNAs in HGSOC. Expression profiles of circRNAs differential expression based on circRNAs High-throughput sequencing were identified in 3 HGSOC specimens and 3 normal ovarian tissues. A total of 710 differentially expressed circRNAs were found (354 expressions up-regulated and 356 expressions down-regulated). CircRNA sequencing data were verified by qRT-PCR in HGSOC tissue and benign ovarian lesions. Differential expression of 7 circRNAs (circRNA385, circRNA2058, circRNA3336, circRNA2606, circRNA1656, circRNA1312 and circRNA7474) in HGSOC tissue was confirmed by qRT-PCR. Among them, circRNA1656 showed the highest fold change. qRT-PCR was used to verify the expression of circRNA1656 in ovarian cancer cell lines. In order to analyze the relationship between circRNA1656 expression and clinical pathological biological characteristics of HGSOC, qRT-PCR was used to verify the expression of circRNA1656 in 60 HGSOC tissues compared with 60 benign ovarian lesions. The expression of circRNA1656 was down-regulated in HGSOC tissues and ovarian cancer cell lines, and correlated with the FIGO stage of HGSOC. circRNA1656 has the potential to serve as a novel tumor marker for HGSOC.
Adhesions due to previous upper abdominal surgery may complicate later liver transplantation. Here we report successful living donor liver transplantation (LDLT) in a patient with a history of total gastrectomy. A 32-year-old Japanese woman developed end-stage liver failure due to alcoholic cirrhosis. She had undergone total gastrectomy, pancreato-splenectomy, and partial colectomy due to rupture of a pancreatic cyst. LDLT was performed using a right lobe graft from her sister. To minimize blood loss and injury to the jejunum, adhesions between the left lobe and nearby organs were dissected without blood flow in or out of the liver. The right liver graft was implanted uneventfully. She was extubated on postoperative day (POD) 1, but then developed septic shock due to aspiration pneumonia on POD 2. She was reintubated and antibiotics and antifungal agents were administered. Administration of tacrolimus was changed to an intravenous route on POD 3. Her condition improved and she was re-extubated on POD 9. On POD 14, tacrolimus was administered orally. She was discharged from our hospital on POD 30 without any other events and is doing well 6 months after LDLT. We believe that careful planning, such as mobilizing the left lobe with the blood flow blocked just before liver explantation, elevating the head of the bed during tube-feeding, and calculating the area under the curve after drug administration will enable liver transplantation for patients with a history of total gastrectomy.