[Improvement of high-quality evaluation criteria of Chinese patent medicines based on whole process control].

Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.

Ultrasoft and Biocompatible Magnetic-Hydrogel-Based Strain Sensors for Wireless Passive Biomechanical Monitoring.

Implantable flexible mechanical sensors have exhibited great potential in health monitoring and disease diagnosis due to continuous and real-time monitoring capability. However, the wires and power supply required in current devices cause inconvenience and potential risks. Magnetic-based devices have demonstrated advantages in wireless and passive sensing, but the mismatched mechanical properties, poor biocompatibility, and insufficient sensitivity have limited their applications in biomechanical monitoring. Here, a wireless and passive flexible magnetic-based strain sensor based on a gelatin methacrylate/Fe3O4 magnetic hydrogel has been fabricated. The sensor exhibits ultrasoft mechanical properties, strong magnetic properties, and long-term stability in saline solution and can monitor strains down to 50 µm. A model of the sensing process is established to identify the optimal detection location and the relation between the relative magnetic permeability and the sensitivity of the sensors. Moreover, an in vitro tissue model is developed to investigate the potential of the sensor in detecting subtle biomechanical signals and avoiding interference with bioactivities. Furthermore, a real-time and high-throughput biomonitoring platform is built and implements passive wireless monitoring of the drug response and cultural status of the cardiomyocytes. This work demonstrates the potential of applying magnetic sensing for biomechanical monitoring and provides ideas for the design of wireless and passive implantable devices.

[Advantages and disadvantages of production quality of Fufang Danshen Prescription based on high-quality Chinese patent medicine evaluation criteria].

The big brand of Chinese patent medicine, Fufang Danshen Prescription(FDP), effective in promoting blood circulation, resolving blood stasis, regulating qi, and relieving pain, is wide in clinical application and diverse in dosage forms and products, but its quality and price are uneven, which causes problems for doctors and patients. To clarify the key links and weakness of quality control leading to the quality difference of FDP products, the present study carried out a comprehensive evaluation of the whole production cycle of FDP based on the "high-quality Chinese patent medicine evaluation criteria" and analyzed the advantages and disadvantages of production and quality of different FDP products according to scores. The results showed that the scores of various products in the "raw materials selection" varied greatly. The highest score(S1) and the lowest score(S2) differed by more than 3 times, indicating that different manufacturers had inconsistent requirements for the selection of raw materials, leading to fundamental differences in the quality of raw materials. The scores in the "production process" varied slightly, with an average score of 66.8%. The manufacturer S8 obtained the highest score(84.0%), which indicated the emergence of intelligent manufacturing production. The scores(with the average score of 44.0%) in the "quality control" were lower than those of the previous two items, which was attributed to the fact that most FDP products only met the "qualified" benchmark required by the 2020 edition of Chinese Pharmacopoeia, and their consistency and high quality were both uncontrollable. The scores in the "post-marketing research" were the lowest(with an average score of 28.5%), and most manufacturers were scored 0, which reflected little attention paid. Only a few brand manufacturers were scored acceptably and they were willing to carry out relevant research on post-marketing evaluation. The evaluation results demonstrated the key links and weakness leading to the production and quality differences of FDP from different manufacturers. It is expected to improve the quality of FDP, promote the formation of the "high quality and good price" mechanism, and provide information for the centralized procurement of governments.

[Evaluation and analysis of high-quality products of Liuwei Dihuang Pills].

Liuwei Dihuang Pills is a typical traditional Chinese medicine with "the same product made by many manufacturers". The quality and price of products made in various factories was different obviously. In this study, the quality differences of Liuwei Dihuang Pills were evaluated over multi-dimensions and throughout the whole production cycle involving raw materials, production process, quality control and post-marketing re-studies based on the "Chinese patent medicine evaluation standard with quality at the core" established earlier by our research group. The research results showed that the product quality of various manufacturers was significantly different, and the product quality was positively correlated with the market shares of enterprises, indicating that enterprises with more market shares paid more attention to product quality; and the sales determined the concern degree of enterprises on products, which was in line with general cognition. During the single-item evaluation of Liuwei Dihuang Pills, the score of raw material selection was relatively low, and the enterprises paid less attention to the initial raw materials. The whole production process was better, and the national compulsory implementation of "Production Quality Management Standard"(GMP) had a positive effect in improving product quality. Quality control could basically guarantee product quality. Intelligent manufacturing promoted by the government was beneficial to ensure product uniformity. The score rate of "quality evaluation" item was basically qualified, which indicated that the quality control level of Liuwei Dihuang Pills was acceptable as a whole, but there was still room for improvement. "Re-evaluation and Brand Construction" had the lowest scores, reflecting that enterprises did not pay enough attention to in-depth study and re-evaluation of "the same product made by many manufacturers". The evaluation results were in line with expectations, provided a reference example for the evaluation of high-quality Chinese patent medicine, a basis for the high-quality and good price of Chinese patent medicine, scientific data for improving medical insurance bidding, and thus facilitated promoting the healthy development of the traditional Chinese medicine industry.

Reduced CENPU expression inhibits lung adenocarcinoma cell proliferation and migration through PI3K/AKT signaling.

CENPU (centromere protein U), a centromere component essential for mitosis, relates with some cancers progression. However, it is not well illustrated in lung adenocarcinoma (LAC). Here, we aimed to investigate the potential effect of CENPU on LAC progression and prognosis. In this experiment, expression level of CENPU and association between its expression and LAC patients' clinicopathological characteristics and prognosis were analyzed. The proliferation, migration and invasive abilities of LAC cells were determined by CCK-8, colony formation, transwell assays. Western blot was used to detect PI3K/AKT signaling key proteins. We found CENPU level was overexpressed in LAC tissues on comparing normal tissues. Moreover, CENPU overexpression correlated with clinicopathological variables and predicted an independent prognostic indicator in LAC patients. Functionally, CENPU downregulation significantly inhibited LAC cell proliferation, migration and invasion in, which was possibly mediated by PI3K/AKT pathway inactivation. Our findings insinuate targeting CENPU may be a potential therapeutic strategy for LAC.

Combination of pulse wave velocity with clinical factors as a promising tool to predict major adverse cardiac events after percutaneous coronary intervention.

BACKGROUND: The relationship between aortic stiffness and coronary artery disease has been proven. Logistic Clinical SYNTAX score (LogCSS), which combined the anatomical evaluation of coronary artery disease and three clinical factors (age, left ventricular ejection fraction, and creatinine clearance), showed improved predictive value for cardiovascular events in patients after percutaneous coronary intervention (PCI). The combination of pulse wave velocity (PWV) and clinical factors may show equivalent predictive value. METHODS: Three hundred and seventy-six patients who were diagnosed with non-ST-segment elevation coronary syndrome (ACS) and showed at least one ≥50% angiographic stenosis in a major coronary artery were enrolled. The Clinical PWV score was calculated by assigning points to different levels of age, creatinine clearance, left ventricular ejection fraction, and carotid-femoral PWV (cfPWV). The points for cfPWV were determined based on the cutoff values of quintiles (model 1) or the relationship between cfPWV and SYNTAX scores (model 2). The predictive values of LogCSS and Clinical PWV score for 3-year major adverse cardiac events (MACE), which were defined as all-cause death, nonfatal myocardial infarction, and nonfatal target vessel revascularization, were analyzed in 298 patients undergoing PCI. RESULTS: The Clinical PWV score based on model 2 demonstrated a similar predictive ability for 3-year MACE compared with LogCSS (AUC 0.72 vs. 0.75; p=0.11). The AUC of LogCSS was significantly higher than the AUC of Clinical PWV score based on model 1 (AUC=0.70, p=0.03). Compared with cfPWV in isolation (AUC=0.61), Clinical PWV score from model 2 showed significantly better predictive power (p=0.03). CONCLUSION: Combination of PWV with age, creatinine clearance, and left ventricular ejection fraction appears to be a promising tool to predict MACE after PCI in patients with ACS.

[Determination of arsenic speciation in Scomberomorus niphonius by capillary electrophoresis-inductively coupled plasma mass spectrometry].

A method for the detection of arsenocholine (AsC), arsenobetaine (AsB), As(III), dimethylarsinic (DMA), monomethylarsonic (MMA) and As (V) by capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) was established. The results showed that the six species of arsenic were separated within 20 min under the optimized conditions. Good linearities of 6 arsenic species were observed in the range from 2 to 50 µg x L(-1) with the linear correlation greater than 0.996, the detection limits were 0.10-1.08 µg x L(-1) and the RSDs (n = 5) of the peak areas were smaller than 7%. The method was successfully adopted to the determination of the species in Scomberomorus niphonius. The recoveries were between 93% and 98%, and we found the arsenobetaine (AsB) was the main species in the sample. The method was suitable for the analysis of other biological samples with the advantages of good stability, less sample consumption, short analysis time and convenience.

The role of cardiac pacing in carotid sinus syndrome: a meta-analysis.

PURPOSE: Cardiac pacing can be used to treat carotid sinus syndrome (CSS), but clinical studies have shown conflicting results. We conducted a systematic review and meta-analysis to evaluate the role of pacing for CSS. METHODS: A systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. Prospective randomized studies that compared cardiac pacing with standard therapy or pacing with different algorithms were included if the recurrence of syncope or the number of falls was observed. RESULTS: Eight studies enrolling 540 patients were identified. In open-label studies, the recurrence of syncope was reduced significantly by cardiac pacing compared with standard therapy. The recurrence of syncope was not different between single- and dual-chamber pacing, but a lower rate of patients with pre-syncope was observed in the group with dual-chamber pacing. Double-blind clinical studies failed to observe the role of cardiac pacing for preventing falls in patients with CSS. CONCLUSION: The results of meta-analysis supported the use of cardiac pacing for patients with dominant cardioinhibitory CSS.

Relationships between use of statins and arterial stiffness in normotensive and hypertensive patients with coronary artery disease.

BACKGROUND: Statins improve arterial stiffness in patients with coronary artery disease (CAD). Hypertension is a predominant contributor of arterial stiffening. However, the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated. Therefore, in this study, we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients. METHODS: Brachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients, including 220 hypertensive CAD patients (121 used statins, 99 did not) and 217 normotensive CAD patients (105 used statins, 112 did not). The normotensive and hypertensive CAD patients were matched according to age, sex, and body mass index (BMI). RESULTS: In the normotensive and hypertensive CAD patients, lipid profiles were significantly improved in the statin group compared with the non-statin group. No significant differences in the administered statins (i.e., atorvastatin, simvastatin, rosuvastatin, and pravastatin) and statin therapy duration were found between normotensive and hypertensive CAD patients (all P > 0.05). No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients, normotensive CAD patients, or hypertensive CAD patients (all P > 0.05). ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients ((1331.68 ± 167.52) cm/s vs. (1468.61 ± 244.54) cm/s, P = 0.002) but not in hypertensive CAD patients (P > 0.05). In multiple linear regression analyses, statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P = 0.018) but not in hypertensive CAD patients (P > 0.05). CONCLUSIONS: Statins may significantly improve arterial stiffness in CAD patients, and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population. Further studies are required to investigate the effect of statins on arterial stiffness in normotensive and hypertensive CAD patients.

[Prevalence, detection, management, and control of hypertension in the population of Mongolian and Han nationalities with age ≥ 55 years in a pastoral area of Inner Mongolia Autonomous Region].

OBJECTIVE: To know about the status of hypertension among Mongolian and Han aged older than 55 years living in pastoral area of the Inner Mongolia Autonomous Region. METHODS: Stratified sampling method was adopted and 9146 people aged 55 years or older were selected, blood pressure measurement and related information were collected, prevalence, awareness, treatment and control rates of hypertension were analyzed. RESULTS: The hypertension crude prevalence rate of Mongolian and Han subjects was 54.10% (standardized prevalence rate was 53.93%), in which, the Mongolian and Han subjects crude hypertension prevalence rate was 52.96% and 54.73% respectively (standardized prevalence rate was 53.44% and 55.08% respectively), and there was no statistically significant (P = 0.104). Among the male gender, awareness rate, treatment rate and control rate of hypertension was 61.03%, 46.73% and 11.87% respectively. Among the female gender, awareness rate, treatment rate and control rate of hypertension was 67.58%, 56.55% and 14.03% respectively. Among Mongolian and Han subjects, difference of hypertension prevalence of different age groups was statistically significant (P values were 0.032 and 0.000), Among Mongolian subjects, difference of hypertension awareness of different age groups was statistically significant (P = 0.000). Among Han subjects, difference of hypertension awareness rates, treatment rates, and control rates of different age groups were statistically significant (P values were 0.000, 0.047 and 0.043). CONCLUSION: Hypertension prevalence rate among Han and Mongolian people older than 55 years living in pastoral area of Inner Mongolia Autonomous Region is high while the awareness, treatment and control rates of hypertension are rather low.

[Determination and distribution patterns analysis of rare earth elements in sediments of Prydz Bay].

A sensitive quantificational method was developed for the analysis of Sc, Y, La, Ce, Pr, Nd, Sm, Eu, etc. in sediments of Prydz Bay by inductively coupled plasma mass spectrometry, and then the REE distribution patterns were analyzed. The samples were digested by microwave using HNO3-H2O2-HF as oxidant. The results showed that the total contents of rare earth elements in eight sites ranged from 117.35 to 348.63 microg x g(-1) and the maximum value was 2.97 times of the minimum value. The REE distribution patterns of different sites in sediments were basically identical and there was an obvious fractionation between LREEs and HREEs. The linear correlation of the method was preferable (r=0.999 7 - 1.000 0). The RSDs (n=3) were no more than 5.0%, and the relative errors were no more than 10%. The detection limits of rare earth elements reached ng x L(-1) level except for Sc. This method was suitable for the analysis of REEs in sediments with the advantages of rapidness, simplicity, high precision and accuracy.

[A prevalence study on mild cognitive impairment among the elderly populations of Mongolian and Han nationalities in a pastoral area of Inner Mongolia].

OBJECTIVE: To understand the epidemiological characteristics and distribution of mild cognitive impairment (MCI) in elderly populations from Mongolian and Han nationalities living in the pastoral areas of Inner Mongolia Autonomous Region of China. METHODS: According to the MCI clinical diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders 4th revised edition (DSM-IV) by American Psychiatric Association, the individuals under study were at the age of 55 or over, with Mongolian or Han ethnicities and living in the pastoral area of Inner Mongolia. RESULTS: The crude MCI morbidity rates of Mongolian and Han of the study populations in the pastoral area of Inner Mongolia Autonomous Region of China was 19.48% (1782/9146) and the standardization morbidity was 18.98%. The crude MCI morbidity rates of both Mongolian and Han ethnicities were 17.46% (the standardization morbidity was 16.99%) and 20.60% (the standardization morbidity was 19.98%), respectively. There showed a significant positive correlation between the crude morbidities and age, also significantly increasing with the latter. In the Mongolian population, the morbidity increased from 12.17% at the age 55-59 to 27.78% at 85 while in the Han population, the morbidity increased from 15.50% at the age 55-59 to 23.53% at 85. In both the populations of Mongolian and Han, there was a statistically difference found between the morbidities of MCI (χ2=13.229, P=0.000). The morbidity was higher in Hans than in the Mongolians. However, there was no statistically significant difference noticed between the morbidities of MCI in the Mongolian males and females (χ2=2.376, P=0.123). There was statistically significant difference found between the morbidities of MCI in the Han males and females, with females having higher risk than males (χ2=24.470, P=0.000). CONCLUSION: The morbidity of MCI in the elderly Mongolian and Han populations from the pastoral area of Inner Mongolia Autonomous Region of China was considered to be quite high and correlated to age and gender.

A clinical study on global TCM therapy in treating senile advanced non-small cell lung cancer.

OBJECTIVE: To assess the clinical efficacy of global traditional Chinese medicine (TCM) therapy in treating senile advanced non-small cell lung cancer (NSCLC), with the aim of seeking a standardized, rational and economical way to treat advanced NSCLC in old patients. METHODS: A retrospective analysis and comparison was carried out in 86 patients with senile advanced NSCLC, 44 treated by global TCM (TCM group) and 42 by chemotherapy (control group) through dynamical observation on related indexes including tumor size, quality of life and the survival time, as well as on the fee for medical service at various time points in the course of the treatment. RESULTS: The changes of tumor size, score of clinical main symptoms and behavior condition (by ZPS scoring), as well as survival rates in the two groups at corresponding time points, were not different significantly (P>0.05). The mean survival time in the TCM group was 13.20+/-1.52 months and that in the chemotherapy group was 13.45+/-1.94 months, showing insignificant difference between them. However, the median survival time in the TCM group (12 months) was actually longer than that in the chemotherapy group (9 months, P<0.05). The mean daily expense and the mean expense (RMB yuan) for each patient in the TCM group were significantly lower than that in the control group, which was 180.73+/-93.21 vs 825.84+/-329.63 for the mean daily expense and 34077.21+/-14638.04 vs 58516.59+/-45429.76 for the mean expense for each patient (both P<0.01). CONCLUSION: Treatment of senile advanced NSCLC with TCM alone has its apparent superiority in stabilizing tumor focus, improving clinical symptoms, elevating quality of life and prolonging the survival time. TCM is also less expensive, making it a good alternative therapeutic approach for this specific group of people.

GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli.

Covalent attachment of polyethylene glycol, PEGylation, has been shown to prolong the half-life and enhance the pharmacodynamics of therapeutic proteins. Current methods for PEGylation, which rely on chemical conjugation through reactive groups on amino acids, often generate isoforms in which PEG is attached at sites that interfere with bioactivity. Here, we present a novel strategy for site-directed PEGylation using glycosyltransferases to attach PEG to O-glycans. The process involves enzymatic GalNAc glycosylation at specific serine and threonine residues in proteins expressed without glycosylation in Escherichia coli, followed by enzymatic transfer of sialic acid conjugated with PEG to the introduced GalNAc residues. The strategy was applied to three therapeutic polypeptides, granulocyte colony stimulating factor (G-CSF), interferon-alpha2b (IFN-alpha2b), and granulocyte/macrophage colony stimulating factor (GM-CSF), which are currently in clinical use.

Ultrasound/microbubble enhances foreign gene expression in ECV304 cells and murine myocardium.

Although viral vectors are efficient systems to transfer foreign genes into cells or target tissues, safety issues remain in relation to human gene therapy. Microbubbles currently used as ultrasound contrast agents have been applied in transfection of genes. This study was designed to test the transfection efficiency and the expression of exogenous gene mediated by ultrasound irradiation enhanced air filled albumin microbubbles in ECV304 cell line in vitro and the heart of the mouse in vivo. Air filled microbubbles (2.0-4.0 microm in diameter) were created by sonicating the mixture of human albumin, glucose, mannitol and special additive that was designed for stabilization. Plasmid DNA loading the reporter genes was gently mixed with microbubbles. The mixture of plasmid DNA and microbubbles was administrated to cultured ECV304 cells and BALB/c mice (tail vein injection) under different ultrasound/microbubble conditions, and then the transfection and expression efficiency were examined. The results both in vivo and in vitro demonstrated that microbubble with ultrasound irradiation could significantly elevate the exogenous gene expression as compared with microbubble or ultrasound only. Overall, the present study showed that the ultrasound-target microbubble destruction method enhanced the exogenous gene expression in vivo and in vitro, and provided a gene therapy way not only efficient but also easy to be manipulated and carried out in clinical.

[Optical parameters of Er3+ in oxyfluoride glass ceramic].

Recently, in virtue of the develop of the semiconductor laser and the doped laser materials with rare-earth ions, the up-conversion laser with resonant pump has became a scientific subject in great demand. The doped oxyfluoride glass ceramic with rare-earth ions is a very excellent material, its optical property and chemical stability are outstanding. So, absorption spectrum of Er3+ in Fluoroxide glass ceramic was measured, and intensity parameters omega lambda were calculated using Judd-Oflet theory. Some predicted spectroscopic parameters of the excited states, like the spontaneous radiative transition rate, branching ratio and integrated emission cross section were given.