AIM To study the chemical constituents form the leaves of Castanopsis orthacantha Fance and their α-glucosidase inhibitory activities.METHODS The methanol extract form the leaves of C.orthacanth was isolated and purified by various column chromatography methods,such as MCI gel CHP 20P,Sephadex LH-20,Diaion HP20SS,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were determined by PNPG method.RESULTS Eighteen compounds were isolated and identified as protocatechuic acid(1),gallic acid(2),3-O-α-L-arabininopyranosyl-4-hydroxybenzoic acid(3),3-O-galloyl shikimic acid(4),methyl 4-epi-shikimate-3-O-gallate(5),5-O-galloyl shikimic acid(6),5-O-caffeoylshikimic acid(7),6-O-galloyl-glucoside(8),1,6-di-O-galloyl-β-D-pyranogluloside(9),1,3-di-O-galloyl-α-D-glucoside(10),2,3-di-O-galloyl-D-glucoside(11),β-O-methylgluco-2,3-digalloyl esters(12),(3R,1'S)-[1'-(6"-O-galloyl-β-D-gluco-pyranosyl)oxyethyl]-3-hydroxy-dihydrofuran-2(3H)-one(13),4-O-D-(6'-O-galloyl)glucopyranyl-(E)-p-coumaryl acid(14),chestanin(15),1-desgalloyl eugeniin(16),picrorhiza acid(17),11-methyl chebulate(18).The IC50 values of compounds 2 and 16 were(0.12±0.059),(0.00089±0.00025)mmol/L,respectively.CONCLUSION All compounds are isolated from the leaves of C.orthacantha for the first time.Compounds 2 and 16 have strong α-glucosidase inhibitory activities.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.
Humans ; Female ; Male ; Osteoarthritis, Knee/therapy* ; Retrospective Studies ; Orthopedic Procedures ; Platelet-Rich Plasma ; Magnetic Resonance Imaging

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.
Artificial Intelligence ; Medicine, Chinese Traditional ; Reproducibility of Results ; Quality Control ; Intelligence ; Pharmaceutical Preparations

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Objective: To establish a sustainable updated literature data warehouse for global vaccine safety assessment, and provide data support for evidence-based vaccine safety assessment. Methods: Semi-automated construction and updating of a literature data warehouse were achieved through the continuous integration of standard operating steps of evidence-based reviews with artificial intelligence technologies. Following the standard procedure of a systematic literature review, the literatures about vaccine safety assessment published before November 29, 2020 were retrieved from 9 databases including OVID, Scopus, Web of Science, Cochrane Library, and ClinicalTrails.org in English and Wanfang, CNKI, VIP, and SinoMed in Chinese. Literatures were screened for two rounds in a semi-automatic manner (by artificial intelligence literature processing system and manual work) according to the inclusion/exclusion criteria. Furthermore, the literatures were classified according to the types of vaccines and adverse events. The updating strategy was established, and the literature data warehouse was updated regularly. Experts were organized to select specific vaccine safety topics and carry out special demonstration studies. Results: More than 0.41 million articles were retrieved. According to the inclusion/exclusion criteria, 23 304 articles were included after two rounds of screening. At present, we have selected and completed three prior topics as demonstration studies, including the systematic review of "DPT (diphtheria, pertussis and tetanus) vaccine and encephalopathy/encephalitis", and the classified management of literatures about allergic purpura and brachial plexus neuritis. Conclusions: The sustainable updated literature data warehouse of vaccine safety can provide high-quality research data for vaccine safety research, including evidence support for immunization related policy-making and adjustment and vaccine safety-related methodological research or clinical tool development; and further demonstration studies can provide references for building a new methodological framework system for timely and efficient completion of the evidence-based assessment of vaccine safety.
Artificial Intelligence ; Data Warehousing ; Humans ; Tetanus ; Tetanus Toxoid ; Whooping Cough/prevention & control*