Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

OBJECTIVE To explore the potential mechanism of the effect of Xuebijing injection （XBJ） on neurological function and survival of rats after cardiac arrest （CA）/cardiopulmonary resuscitation （CPR） based on the S-nitrosoglutathione reductase （GSNOR）/S-nitrosoglutathione （GSNO） pathway. METHODS The CA/CPR rat model was established by ventricular fibrillation. Using a sham operation group as control， high-throughput sequencing was employed to analyze and mine the differentially expressed genes （DEGs）. Enzyme-linked immunosorbent assay was used to determine the contents of GSNOR and GSNO in the hippocampus； the active components of XBJ were screened and subjected to molecular docking analysis with GSNOR. The rats successfully modeled using the same method were divided into model group （n＝30）， inhibitor （GSNOR inhibitor） group （n＝30）， XBJ group （n＝30） and XBJ+inhibitor group （n＝30）， and a sham operation group （n＝30） was set up. Neurological function was evaluated and survival status was recorded at 3 hours， 24 hours and 3 days after the first 89） drug intervention. The contents of GSNOR and GSNO in the hippocampus of rats were determined in each group at the 0191） above time points， and the relationship of the contents of GSNOR and GSNO with modified neurologic severity scale （mNSS） score was analyzed. RESULTS GSNOR coding gene was differentially expressed between the model group and the sham operation group. Compared with the sham operation group， GSNOR content increased significantly in the hippocampus of rats in model group， while GSNO content decreased significantly （P＜0.05）. The active components of XBJ， such as 4- methylenemiltirone and salviolone， could be bound to GSNOR protein， with the binding energy lower than －6 kcal/mol， mainly connected by hydrogen bonds. Animal experiments revealed that mNSS score and GSNOR levels in the hippocampus of rats in the model group were significantly higher than those in the sham operation group （P＜0.05）， while GSNO levels and survival rate were significantly lower than those in the sham operation group （P＜0.05）. The above indexes of rats were improved significantly in administration groups， the mNSS score in the XBJ group was significantly lower than that in the inhibitor group， the content changes of GSNOR and GSNO in the inhibitor group were more obvious than those in the XBJ group， and the various indicators in the XBJ+inhibitor group were significantly better than the XBJ group and the inhibitor group （P＜0.05）. GSNOR content was positively correlated with the mNSS score， and GSNO content was negatively correlated with the mNSS score （P＜0.05）. CONCLUSIONS XBJ can improve the neurological function of rats and enhance their survival rates after CA/CPR， the mechanism of which may be associated with the down-regulation of GSNOR and the up-regulation of GSNO.

Objective: To analyze the characteristics of influenza virus detection in an influenza outbreak in schools, so as to provide a strategic basis for the treatment of influenza outbreaks in schools. Methods: A total of 1 702 samples were collected from 52 school influenza outbreaks reported in Linyi City in 2021-2022. The samples were divided into 3 types according to different symptoms during the management of the epidemic [group A:influenzalike illness (ILI) group; group B:mild illness group; group C:close contacts group]. Rt-PCR was used to detect influenza virus nucleic acid in the collected samples. The detection rate of influenza virus in the outbreaks was analyzed by χ2 test. Results: In total, 1 071 samples (62.93%) tested positive for influenza virus nucleic acid. Among them, 610 out of 726 samples (84.02%) were detected in group A, while 331 out of 634 samples (52.21%) were detected in group B. In group C, 130 out of 342 samples (38.01%) tested positive. The differences were statistically significant (χ2=260.71, P<0.01). In group A, males had a detection rate of 80.83% for influenza virus nucleic acid, compared to 91.36% for females. For group B, the rates were 53.31% for males and 50.87% for females. In group C, males had a rate of 30.72%, while females had a rate of 43.92%. Statistical significance for gender differences was observed only in groups A and C (χ2=12.67, 6.25, P<0.05). According to the days of onset, the detection rates of influenza virus nucleic acid among patients with onset 0-6 days were 56.30%, 74.49%, 89.35%, 86.23%, 69.67%, 62.75%, 34.33%, respectively, and the difference was statistically significant (χ2=128.27, P<0.01). Conclusions Mild cases and close contacts are likely key factors contributing to the prolonged emergence of new cases within classrooms during school influenza outbreaks. The progression of influenza symptoms is related to the risk of transmission.

ObjectiveTo understand the usage of antibiotics in outpatients in a county of Zhejiang Province from 2015 to 2020， so as to provide a basis for further standardizing the clinical application of antibiotics in this region. MethodsOutpatient records and prescription records of 146 public medical institutions from 2015 to 2020 were extracted from the electronic medical record data sharing platform system of medical institutions in a county of Zhejiang Province. The utilization rates and the number of types of antibiotics used in outpatient patients were described. According to the drug anatomy， therapeutic and chemical classification system （ATC）， clinical application classification and dosage form， the use status of different types of antibiotics was observed. The annual percentage change （APC） was used to analyze the time trend of antibiotic use. Among the antibiotic prescriptions in each year， the proportions of prescriptions aimed for different use reasons and patients were compared to analyze the changes in the structures of antibiotic prescriptions. ResultsDuring 2015‒2020， a total of 2 861 438 prescriptions were issued in146 primary public medical institutions in this county， including 314 642 prescriptions for antibiotics， and the overall utilization rate of antibiotics was 11%. The utilization rate of antibiotics showed a decreased trend across the years （from 14.23% in 2015 to 7.59% in 2020，APC=-11.51%， 95%CI=-0.01%‒-21.7%， t=-12.05， P<0.001） and an obvious seasonal variation character （higher in winter and spring， lower in summer and autumn）. Cefoxitin sodium for injection was the most used antibiotic in 2015， and cefuroxime was the most used antibiotic from 2015 to 2020， respectively. The utilization rates of cephalosporins （APC=-11.06%， 95%CI=0‒-20.89%， t=-22.233， P<0.001）， quinolones （APC=-9.74%， 95%CI=0‒-18.53%， t=-7.652， P=0.002）， macrolides （APC=-17.52%， 95%CI=0‒-17.52%， t=-3.626， P=0.022） and lincoamides （APC=-49.01%， 95%CI=0‒-74%， t=-3.35， P=0.029） showed a decreasing trend across the years. There were differences in the distribution of drug use reasons （χ²=9 458.427， P<0.001）， as well as the age （χ²=5 421.709， P<0.001） and sex （χ²=245.322， P<0.001） of patients. During the observation period， 50.69% of antibiotic prescriptions were used to treat respiratory diseases， with the highest proportion of 57.67% in 2015 and the lowest proportion of 34.93% in 2020. 58.37% of patients were aged 50‒70 years， with a decreasing proportion of patients under 50 years （17.83% in 2015， 6.64% in 2020） and an increasing proportion of patients over 70 years （24.1% in 2015， 38.41% in 2020）. ConclusionThe utilization rate of antibiotics used in outpatients from primary public medical institutions in a county of Zhejiang Province shows a decreasing trend across the years， but higher than that of secondary and above hospitals in China， and also higher than that of primary medical institutions in economically-developed areas. The management and monitoring of the clinical use of antibiotics in the county should be actively strengthened.

Objective:To understand the pathogenic situation of hand, foot and mouth disease (HFMD) in Linyi City, and to analyze the gene characteristics of Coxsackievirus A10 complete VP1 region.Methods:The samples of HFMD cases from Linyi City in 2023 were tested for typing and strain isolation, and the VP1 gene of CV-A10 isolate was amplified and sequenced. The obtained sequences were compared with those in the NCBI database, and the phylogenetic tree was constructed for gene characteristics and molecular epidemiological analysis.Results:In 2023, a total of 861 samples of HFMD were collected, and 594 (68.99%) were positive for nucleic acid tests. The male to female ratio of positive cases was 1.56∶1. Children under 5 years old accounted for 81.65%, and the highest incidence season was from June to August (83.84%). CV-A6 was the main pathogen (84.51%), followed by CV-A10 (9.93%). The nucleotide and amino acid homology of VP1 gene sequence among 13 isolates were 93.29%-100.00% and 97.65%-100.00%, respectively. The nucleotide and amino acid homology with AF081300-Kowalik/USA/1950 was lower (75.95%-76.62%, 91.72%-92.41%). The amino acid and nucleotide homology with C2c was the highest (94.28%-96.76%, 98.28%-100.00%), and the genetic distance was the closest (0.04-0.06). Amino acid site variation analysis showed that compared with the prototype strain AF081300-Kowalik/USA/1950, the isolates had more site variation, while only some isolates had I80V, E141K, P147S, T219I, E240K and V261I mutations compared with the representative strain C2c. The genetic evolution tree showed that the isolates were all in the same clade as the C2c representative strains, and they all belonged to the C2c genotype, and the isolates were further divided into two smaller clades.Conclusions:In 2023, CV-A6 was the main pathogen of HFMD in Linyi City, followed by CV-A10. All CV-A10 isolates were C2c genotypes and can be divided into two evolutionary clades. Continuous monitoring and genetic characterization of CV-A10 should be strengthened.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Small integral membrane protein 1(SMIM1) gene encodes Vel blood group antigen, and homozygous deletion of 17 bases pairs in its exon 3 leads to Vel negative phenotype. As a rare phenotype, accurate identification and prevention of transfusion reaction for Vel negative phenotype is particularly important. In addition to serving as a Vel blood group antigen, recent bioinformatics analysis suggests that SMIM1 protein may be a new tumor biomarker involved in the occurrence and development of numerous tumors. Due to the similarity in structure between SMIM1 protein and glycoprotein, and its phosphorylation in red blood cells infected with Plasmodium falciparum, it is speculated that SMIM1 protein may be involved in the development of malaria. Therefore, this article provides a review of the related research on SMIM1 and its coding protein in Vel blood type, tumor and plasmodium infection.

Reasonable use of antispasmodics to attenuate gastrointestinal peristalsis during digestive endoscopy is an effective clinical strategy to improve the clarity of endoscopic images and diagnostic accuracy. The commonly used antispasmodics in gastroenteroscopy mainly include systemic antispasmodics and local antispasmodics at present. Systemic antispasmodics have some limitations, such as inconvenience in usage, many contraindications and adverse reactions. Local antispasmodics can act directly on the digestive tract mucosa by oral administration or spraying, which can quickly and effectively inhibit peristalsis, and is convenient for clinical use with fewer adverse reactions. This review summarizes the mechanism of action, efficacy and application of systemic antispasmodics and local antispasmodics in digestive endoscopy, in order to provide strategies for the selection of antispasmodics in digestive endoscopy.

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

OBJECTIVE To investigate the effects of pharmacological inhibition of STING by C-176,a STING selective inhibitor,in experimental model of Parkinson's disease.METHODS The acute and sub-acute mice mod-els of Parkinson's disease(PD)were established by in-traperitoneal injection of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine(MPTP).The selective STING inhibitor C-176 was administered by intraperitoneal injec-tion.The potential neuroprotective effects of C-176 were evaluated by behavioral test,tyrosine hydroxylase(TH)immunostaining,Nissl staining,Western blotting,qPCR and immunofluorescence.For in vitro study,the effects of C-176 on LPS/MPP+-induced inflammatory responses in BV2 microglial cells were determined by real time RT-PCR and Western blotting analysis.RESULTS Our study revealed that C-176 significantly inhibited STING signaling activation,ameliorated MPTP-induced dopami-nergic neurotoxicity,motor deficit and associated neuroin-flammation.Furthermore,pharmacological inhibition of STING in BV2 microglia treated with LPS/MPP+ exhibited decreased inflammatory responses.More importantly,C176 also reduced NLRP3 inflammasome activation both in vitro and in vivo.CONCLUSION The results of our study suggest that pharmacologic inhibition of STING protects against neuroinflammation that may act at least in part through suppressing NLRP3 inflammasome acti-vation and thus ameliorated dopaminergic neurodegener-ation.STING signaling may holds great promise for the development of new treatment strategy for PD as an effective therapeutic target.