Objective To determine the median effective dose(ED50)of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method.Methods This is a prospective clinical study.Pediatric patients scheduled for elective short surgery(surgery time≤1 h)under general anesthesia from January to July 2023 were selected.Inclusion criteria were age 1-6 years,an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale(PSAS)score≥3 points.Remimazolam was administered intravenously preoperatively,and its sedative effect was assessed.The modified Dixon sequential method was used to determine the ED50 of remimazolam,with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg.Sedation was considered successful(positive,included in positive group)if the child with sedation score≥2 points,preoperative PSAS score<3 points,and the mask acceptance score of 4 points during anesthesia induction.If any criterion was not met,sedation was considered failure(negative,included in negative group),and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage.The test was completed after 7 consecutive positive and negative turning points appeared alternately.Probabilistic unit regression analysis was used to determine the ED50,ED95 and the corresponding 95%confidence interval(CI)of remimazolam for preoperative sedation.Postoperative recovery time and adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting during anesthesia were recorded.Results A total of 23 pediatric patients were included,with 13 in positive group and 10 in negative group.There were no statistically significant differences in mean arterial pressure,pulse oxygen saturation or heart rate before and after sedation(P>0.05).Compared with negative group,positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia(P<0.05).There was no significant difference in sedation score and anesthesia awakening time between two groups(P>0.05).The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg(95%CI 0.033-0.065 mg/kg),and the ED95 was 0.077 mg/kg(95%CI 0.064-0.161 mg/kg).No adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting occurred during anesthesia in any of pediatric patients.Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg(95%CI 0.033-0.065 mg/kg).

Protein phosphorylation modification is one of the key regulatory mechanisms in cellular signaling transduction and metabolic processes. The phosphorylation state of target proteins is regulated by specific protein kinases and phosphatases, which add or remove phosphate groups. Histidine phosphorylation (pHis) plays a crucial role in both prokaryotes and eukaryotes life activities and is linked to various pathological processes. Unlike the stable phosphorylation of proteins via phosphate ester bonds, histidine phosphorylation is linked through phosphoramide bonds, making it highly sensitive to high temperatures and low pH. This sensitivity has historically impeded progress in identifying and studying histidine phosphorylation. In recent years, the development of new techniques in phosphoproteomics and the emergence of pHis-specific antibodies have promoted the identification and functional research of pHis-modified substrates. For the first time, more than 700 pHis-modified proteins have been identified in mammalian cells, and pHis-modified substrates such as focal adhesion kinase (FAK) and phosphoglycerate mutase 1 (PGAM1) have been found to promote tumor development. This article mainly reviewed the key mechanisms and functions of histidine kinases and histidine phosphatases in regulating the histidine phosphorylation of specific substrates, and highlights their significant roles in human physiological and pathological processes, aiming to provide guidance for further research into the biological functions of histidine phosphorylation.

In order to improve the poor photostability of nifedipine, this study designed a cocrystal based on the principles of crystal engineering and prepared nifedipine-imidazole cocrystal by suspension method. The new cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and infrared spectroscopy (IR) to confirm the formation of the cocrystal. The photostability of nifedipine and its cocrystal was measured by powder X-ray diffraction and high-performance liquid chromatography (HPLC). The results showed that the nifedipine-imidazole cocrystal improved the photostability of nifedipine to a certain extent. This study provides guidance for the development of nifedipine cocrystals and the improvement of its druggability.

Objective: To assess the cardiovascular health status of adults in China by using the "Life's Essential 8" score, and provide reference for the development and improvement of cardiovascular disease prevention and control policies and measures. Methods: Chronic Disease and Nutrition Surveillance was conducted in 298 counties/districts in 2015 in 31 provinces (autonomous regions, municipalities) across China, multi-stage stratified cluster random sampling was used to select 45 households in each village or neighborhood, and 20 households were further selected to conduct dietary surveys. In this study, a total of 70 093 adults aged ≥20 years who completed the dietary survey and had complete information were included, their cardiovascular health status were assessed by using the "Life's Essential 8" score, a cardiovascular health scoring standard released by the American Heart Association in 2022. All results were adjusted using complex design-based sampling weights to achieve a better estimate of the population. Results: In 2015, the overall cardiovascular health score of Chinese adults aged ≥20 years was 73.3±12.6, the score was significantly higher in women (77.9±11.6) than in men (68.7±11.8), and higher in urban area (74.5±12.8) than in rural area (71.9±12.2), the differences were significant (P<0.001). It was estimated that about 0.25% (95%CI: 0.16%-0.33%) of adults in China had cardiovascular health score of 100, and 33.0% (95%CI: 31.6%-34.3%), 63.2% (95%CI: 62.1%-64.3%), and 3.9% (95%CI: 3.5%-4.2%) of adults had high, moderate and low cardiovascular health scores, respectively. The proportion of those with high cardiovascular health scores was relatively low in men, those with low education level, those with low income, those living in rural areas, and those living in southwest China (P<0.001). Of the eight factors, diet had the lowest mean score (46.0, 95%CI: 44.7-47.3), followed by blood pressure (59.4, 95%CI: 58.2-60.6) and tobacco exposure (61.4, 95%CI: 60.6-62.2). Conclusions: The cardiovascular health status of two-thirds of adult population in China needs to be improved. Diet, tobacco exposure, and blood pressure are the factors affecting the cardiovascular health of Chinese population, to which close attention needs to be paid, and men, rural residents, and those with lower socioeconomic status are key groups in cardiovascular health promotion.
Adult ; Female ; Humans ; Male ; Asian People ; Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Diet ; East Asian People ; Health Status ; Risk Factors ; United States ; Young Adult ; Health Status Indicators

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

Objective: To analyze the blood pressure measurement of Chinese adult residents in 2018 and provide a scientific basis for early detection and intervention of hypertension. Methods: In 2018, China Chronic Disease and Risk Factor Surveillance were conducted in 298 counties (districts) of 31 provinces (autonomous regions, municipalities) across the country, using a multi-stage stratified cluster random sampling method to survey permanent residents aged 18 years and above. We selected 184 509 people and carried out a face-to-face questionnaire survey and body measurement method to collect demographic data, major chronic diseases, and blood pressure measurement information of the survey subjects. Blood glucose and blood lipid-related indicators were obtained by laboratory testing. There were 170 551 adult residents included in the study after excluding abnormal and missing data for key variables. After complex weighting, blood pressure detection rates and detection times in people with different blood pressure levels and other diseases were analyzed. SAS 9.4 software was used to perform the χ²-test and trend test. Results: Among adult residents in China, the proportions of those with normal blood pressure, commonly recognized 'high' blood pressure, and newly detected hypertension who had their blood pressure tested within three months were 44.4%, 50.4%, and 52.6%, respectively. The proportions all appeared higher in women than in men (all P<0.05), in urban than in rural areas (all P<0.05), and showed an increasing trend with age (all P<0.001); The proportion of these three populations who had never had their blood pressure measured was 27.6%, 24.2%, and 23.5% respectively. The proportion of people with diagnosed hypertension who had their blood pressure tested within seven days was 44.0%, 51.4% in urban areas, higher than 37.7% in rural areas (P<0.001), and the proportion of people who had their blood pressure tested increased with education, per capita annual income and BMI (all P<0.001). Conclusions: The behavior of regular self-monitoring of blood pressure among adult residents in China still needs to be improved, especially among men and rural areas. Relevant health promotion and education should be strengthened. More targeted policies and measures should be developed to improve blood pressure measurement behavior in people with normal high blood pressure and other high-risk groups to control elevated blood pressure effectively.
Adult ; Asian People ; Blood Pressure ; Blood Pressure Determination ; China/epidemiology* ; Female ; Humans ; Hypertension/epidemiology* ; Male ; Rural Population

Objective: To understand the awareness of weight and waist circumference and their influencing factors among residents aged ≥18 years in China and provide a reference for the development of relevant prevention and treatment policies and evaluation of intervention effects. Methods: We selected 298 counties (districts) from the 31 provinces (autonomous regions and municipalities) which participated in the 2018 China Chronic Disease and Risk Factor Surveillance program and included 194 779 permanent residents aged ≥18 years. To obtain the demographic characteristics of the study population, we used a multi-stage stratified whole-group random sampling method, questionnaires, and physical measurements. In this study, 179 045 people who completed the survey and had complete information on weight and waist circumference awareness were used as the study subjects. The weight awareness rate and waist circumference awareness rate were calculated by gender stratification, age, urban-rural, and education level groups. A multi-factor logistic regression model was used to analyze the influencing factors related to weight and waist circumference awareness of residents aged ≥18 years. Results: The weight awareness rate of adult residents in China in 2018 was 45.4% (95%CI: 41.9%-48.9%), higher among men [46.2% (95%CI: 42.5%-49.8%)] than women [44.6% (95%CI: 41.1%-48.2%)], and in urban areas [54.3% (95%CI: 49.3%-59.3%)]. The highest weight awareness rate appeared in residents with low BMI grouping [49.9% (95%CI: 44.3%-55.6%)], and the weight awareness rate in residents with undiagnosed central obesity, hypertension, and diabetes was higher than that of residents with diagnosed diabetes, with statistically significant differences (P<0.05). The waist circumference awareness rate of adult residents was 11.6% (95%CI: 9.7%-13.4%), higher in women [12.8% (95%CI: 10.8%-14.8%)] than in men [10.3% (95%CI: 8.6%-12.0%)], higher in urban [14.6% (95%CI: 11.7%-17.4%)] than in rural [8.3% (95%CI: 6.5%-10.2%)], and the waist circumference awareness rate was higher among residents with confirmed diabetes than those with undiagnosed diabetes, with statistically significant differences (P=0.020). The difference was statistically significant (P<0.001). The weight and waist circumference awareness rate increased with education level and annual per capita household income. Multi-factor logistic regression analysis suggested that urban, highly educated, high per capita annual household income and health check-up residents may have higher weight and waist circumference awareness rates among adult residents in China. Conclusion: Less than half of the adult residents in China know their weight status, and only about one-tenth know their waist circumference. Rural residents, those with low education levels and low annual per capita household income, and those who are obese need to be given prioritized attention. The relevant government departments should strengthen the popularization of the importance of weight and waist circumference on health and improve the awareness of our residents about their waist circumference and weight.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Diabetes Mellitus ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight ; Prevalence ; Risk Factors ; Waist Circumference

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Humans ; Noncommunicable Diseases/epidemiology* ; China/epidemiology*

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.