Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective:To analyze the iodine nutritional status of children aged 8 - 10 in Tongren City, Guizhou Province, and provide a basis for scientific iodine supplementation for children.Methods:From 2020 to 2022, a systematic sampling method was adopted in 10 districts and counties of Tongren City. Each year, each district and county was divided into 5 districts based on east, west, south, north, and center. One township (street) was selected from each district, and 40 non boarding students aged 8 to 10 were selected from each township (street) to measure the iodine content of household salt and urine samples. The content of salt iodine in children of different yesas as well as the distribution of urine iodine in children of different districts and counties and different genders were analyzed and compared. Additionally, B-ultrasound was used to measure the thyroid volume of some children and the situation of thyroid enlargement was analyzed.Results:From 2020 to 2022, a total of 6 000 salt samples were collected and monitored from children's households, and 5 989 samples of iodized salt were detected, the coverage rate of iodized salt was 99.8%; and 5 750 samples of qualified iodized salt were found, the qualified rate of iodized salt was 96.0%, the consumption rate of qualified iodized salt was 95.8%; and the median salt iodine was 27.3 mg/kg, the difference in the median salt iodine among children between different years was statistically significant ( H = 10.04, P < 0.001). A total of 6 000 urine samples from children were tested, the median urinary iodine was 225.2 μg/L, the median urinary iodine among children in different districts and counties were statistically significantly different ( H = 85.73, P < 0.001); 3 077 male and 2 923 female urine samples were tested, and the median urinary iodine between different genders was statistically significant different ( Z = - 67.10, P < 0.001). The median urinary iodine of male samples were higher than those of female samples(227.8 vs 222.9 μg/L). The thyroid gland of 2 000 children was examined, and the rate of goiter was 1.0% (21/2 000). Conclusions:From 2020 to 2022, the consumption rate of qualified iodized salt, urinary iodine content and goiter rate of children in Tongren City have all met the national standard for eliminating iodine deficiency disorders. The overall iodine nutrition level exceeds the appropriate amount (urinary iodine of 200 - 299 μg/L).

AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective: To retrospectively analyze the epidemiological characteristics of supernumerary teeth in patients aged 4-18 years old and the influencing factors on the selection of anesthesia methods, and to provide a reference for the selection of anesthesia plans for children and adolescents with supernumerary teeth. Methods: This study is a retrospective study approved by the Institutional Ethics Committee. Based on clinical electronic medical record system and cone beam CT (CBCT) data, a retrospective analysis was conducted on 2 210 patients 4-18 years of age who underwent supernumerary tooth extraction at the School of Stomatology, Fourth Military Medical University from August 2019 to July 2021. Inclusion criteria: ① Age 4-18 years old; and ② The American Society of Anesthesiologists (ASA) classifies anesthesia into grades I-II; and ③ Have complete oral and anesthesia case records and relevant imaging data. Exclusion criteria: ① Incomplete medical records or unclear imaging data; and ② Patients with ASA grade II or above. Patients’ gender and age, the number of supernumerary teeth, arch, location, orientation, eruption status, reason for appointment, anxiety level, degree of cooperation, anesthesia method, and other relevant information were collected and statistically analyzed. Results: A total of 1 865 eligible patients were included, with an average age of (8.9±3.2) years old. There were more male patients (71.37%, 1 331 cases) than female patients (28.63%, 534 cases) (P < 0.001), with a gender ratio of 2.49:1. The majority of supernumerary teeth were single (75.97%, 1 417/1 865), primarily located in the maxilla (97.2%, 1 812/1 865) and the anterior dental region (94.2%, 1 757/1 865), and in a centric position (77.3%, 1 442/1 865). The majority of patients with erupted supernumerary teeth were active in seeking treatment (97.67%, 335/343). Patients with supernumerary teeth located in the maxilla and mandible bones, as well as in the nasal floor, were mainly referred to the department for diagnosis, accounting for 94.38%(1 361/1 442) and 90.00% (72/80) (χ2=1 363.24, P < 0.001), respectively. Regarding anesthesia methods, the largest proportion of patients received nitrous oxide sedation-assisted local anesthesia or nerve block anesthesia, accounting for 38.07% (710/1 865), followed by local anesthesia, accounting for 35.23% (657/1 865). The proportion of patients receiving midazolam intravenous sedation with local anesthesia or nerve block anesthesia and general anesthesia was relatively small, accounting for 20.86% (389/1 865) and 5.84% (109/1 865). Patients 13-18 years of age with supernumerary teeth in the mandibular and posterior regions and without anxiety had the highest proportion of local anesthesia use (P < 0.001). In contrast, patients who had supernumerary teeth located at the base of the nose (50%), severe anxiety (94.12%), and poor cooperation (98.18%) had the highest proportion of general anesthesia use (P < 0.001). There was no significant difference (P = 0.35) in the incidence of intraoperative and postoperative complications after the extraction of supernumerary teeth. However, the proportion of anesthesia-related complications, such as dizziness, coughing, and respiratory depression, occurring in patients who received general anesthesia was higher than local anesthesia, accounting for 3.81% (P = 0.006). Conclusion There is a gender difference in the incidence of supernumerary teeth in patients 4-18 years of age, with a higher prevalence in males. The majority of supernumerary teeth are single and located in the maxillary anterior region, predominantly in a centric position. Patients whose teeth had erupted were more likely to seek medical treatment voluntarily, while patients with supernumerary teeth located in the maxilla and mandible bones, as well as in the nasal floor were more likely to be referred to the department. Patients with high levels of anxiety, poor cooperation, young age, multiple teeth, and high surgical difficulty were more inclined to choose general anesthesia.

Objective To study the synergistic effects of gentiopicroside combined with pabolizumab on photodynamic therapy in mice with breast cancer.Methods MCF-7 cells were injected subcutaneously to establish a tumor bearing mouse model of breast cancer and were randomly divided into model group,control group,positive control group,experimental group and combination group,with 10 mice in each group.The control group was intraperitoneally injected with 50 mg·kg-1 of 5-aminolevulinic acid and irradiated with 200 J·cm-2 laser for 20 min,once a week.The positive control group was intraperitoneally injected with 100μg·kg-1 pabolizumab,twice a week,and photodynamic therapy once a week,the experimental group was intragastric given 100 mg·kg-1 gentiopicroside,once a day,and photodynamic therapy once a week,the combined group was intraperitoneally injected with pabolizumab(100 μg·kg-1),twice a week,and gavage of gentiopicroside(100 mg·kg-1)once a day and photodynamic therapy once a week.Five groups of mice were given the drug for 3 weeks.The tumor inhibition rate of each group was compared,and the levels of interleukin(IL)-12,interferon(INF)-γand tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.The levels of B-cell lymphoma-2 associated gene(Bax),B-lymphoblastoma-2 gene(Bcl-2)and vascular endothelial growth factor(VEGF)protein in tumor tissues were determined by Western blot.Results The tumor inhibition rates of control,positive control,experimental and combined groups were(22.38±2.26)％,(42.27±3.21)％,(38.16±2.17)％and(60.24±2.84)％,respectively.The serum IL-12 levels of model,control,positive control,experimental and combined groups were(127.13±1.25),(132.29±2.31),(155.27±1.48),(163.31±2.67)and(185.24±1.71)pg·mL-1;INF-γ levels were(724.16±3.63),(891.12±4.45),(1 043.19±3.85),(1 082.34±4.51)and(1 492.13±6.57)pg·mL-1;TNF-α levels were(83.81±4.52),(65.26±3.77),(41.07±3.85),(43.59±3.94)and(27.12±3.93)pg·mL-1;the relative protein expression levels of Bax were 0.30±0.08,0.47±0.05,0.67±0.11,0.89±0.06 and 1.03±0.10;the relative protein expression levels of Bcl-2 were 0.99±0.04,0.86±0.06,0.71±0.05,0.46±0.06 and 0.31±0.08;the relative protein expression levels of VEGF were 1.06±0.04,0.92±0.03,0.76±0.04,0.49±0.04 and 0.29±0.08.The differences of above indexes between the combined group and the control,positive control group and experimental groups were statistically significant(all P＜0.05).Conclusion Gentiopicroside combined with pembrolizumab can significantly enhance the tumor inhibition effect of photodynamic therapy on breast cancer mice,promote the apoptosis of breast cancer cells,and then inhibit the tumor progression of breast cancer mice.

Objective To investigate the efficacy of flupentixol combined with ondansetron in preventing postoperative nausea and vomiting(PONV)in patients receiving sufentanil and dezocine patient-controlled intravenous analgesia(PCIA).Methods Surgical patients receiving sufentanil and dezocine PCIA were randomly divided into treatment and control groups using a random number table.The control group received sufentanil 150 μg,dezocine 20 mg,and ondansetron 8 mg for PCIA,while the treatment group received sufentanil 150 μg,dezocine 20 mg,flupentixol 5 mg,and ondansetron 8 mg for PCIA.The incidence of PONV,severity of PONV,heart rate(HR),mean arterial pressure(MAP),blood oxygen saturation(SPO2)levels at different time points after surgery,surgery-related indicators,visual analogue scale(VAS)scores,Ramsay scores,PCIA pressing times,and incidence of adverse drug reactions were compared between the two groups.Results The incidence of PONV in the treatment group and the control group at 2,12,24,36 and 48 hours after surgery were 1.64％,4.84％,6.56％,3.28％,0 and 14.75％,18.03％,19.67％,16.39％,9.84％,respectively.The HR at 24 hours after surgery in the treatment group and the control group were(91.42±8.75)and(98.13±9.62)beat·min-1,respectively;the MAP were(91.98±4.56)and(99.05±4.17)mmHg;SPO2 were(98.13±1.65)％and(98.95±1.82)％;VAS scores were 2.68±0.49 and 2.97±0.63;Ramsay scores were 2.27±0.65 and 2.05±0.32;PCIA pressing times were(2.14±0.37)and(4.36±0.78)times,respectively.The differences in the above indicators between the treatment group and the control group were statistically significant(all P＜0.05).The incidence of total adverse drug reactions after surgery in the treatment group and the control group were 13.12％and 8.20％,respectively,with no statistically significant difference(P＞0.05).Conclusion Flupentixol combined with ondansetron can reduce the risk of PONV caused by sufentanil combined with dezocine PCIA after surgery,ensuring good analgesic effects and safety.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.