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.

Primary hyperoxaluria type 3 (PH3) is a rare monogenic nephrolithiasis caused by HOGA1 gene mutations. With the advancement of technology of genetic testing, the mutation site of PH3 patients can be clearly located, and the characteristics of genotype, phenotype, genotype-phenotype correlations are also gradually recognized. With the development of gene therapy, novel gene editing techniques and RNA interference treatments offer hope for the future of PH3 treatment. In this paper, the characteristics of genotype and phenotype, genotype-phenotype correlations of PH3 will be summarized and its future treatment will be prospected.

Objective:To explore the operational accuracy and operative time of oral surgery robot-assisted endodontic microsurgery on a head-simulator for clinical reference.Methods:Three pairs of surgical simulation models were set up on head-simulator. Each model included 10 positions anteriorly and posteriorly, 20 teeth for each technique, for a total of 60 teeth. An attending physician with more than 3 years clinical experience in endodontic microsurgery completed fixed-point osteotomy and apicoectomy in three groups of endodontic microsurgery under freehand (FH), static navigation (SN), and surgery robot (SR). The duration of each operation was recorded. Cone-beam CT was taken before the operation and the surgical path was planned in the software; after surgery, a plug gauge (precision gauge for measuring hole dimensions) was inserted into the surgical path for intraoral scanning. Surgical accuracy (starting point, end point, and angular deviation) was assessed in all 3 groups, and surgery time was compared.Results:The deviation at the starting point and the end point, and angular deviation was (0.37±0.11), (0.37±0.10) mm, and 0.71°±0.17°in the SR group. The deviations in the SR group were significantly lower than those in the SN group [(0.59±0.14), (0.65±0.18) mm, and 2.64°±0.75°] ( P<0.05), and both groups were significantly lower than the FH group [(1.37±0.31), (1.10±0.21) mm, and 9.84°±3.15°] ( P<0.05). The operative time in the SN group [(1.20±0.03) min] was significantly less than that in the SR group [(2.18±0.03) min] ( P<0.05), and both groups were significantly less than that in the FH group [(8.70±3.15) min] ( P<0.05). Starting point deviation, end point deviation, and angular deviation [(1.09±0.10), (0.90±0.07) mm, 7.22°±1.13°] in anterior teeth using the FH was significantly lower than the starting deviation, endpoint deviation, and angular deviation [(1.65±0.14), (1.30±0.06) mm, 12.46°±2.10°] in the posterior teeth using FH ( P<0.05), and the operative time in the anterior teeth using the FH [(5.75±0.57) min] was significantly less than that in the posterior teeth using [(11.65±1.14) min] ( P<0.05). The difference in accuracy and operative time between using SN and SR on anterior and posterior teeth was not statistically significant ( P>0.05). Conclusions:Oral surgery robot-assisted endodontic microsurgery helps improving the accuracy of clinicians′ operations and shorten the operation time.

Objective To explore the strategy of intrathoracic anastomosis in patients with esophageal squamous cell carcinoma when the proximal esophagus is dilated to different degrees and explore its mechanism. Methods We retrospectively reviewed the clinical data of patients who underwent esophagectomy between 2014 and 2017 in West China Hospital. The patients were divided into two groups including a significant dilatation group with inner mucosal phase diameter (IMPD)≥17.9 mm and a non-significant dilatation group with IMPD<17.9 mm. And the patients were divided into two groups (a layered manual anastomosis group and a stapled anastomosis group) according to anastomosis method and propensity score matching was applied to adjust for potential confounders. Results We finally included 654 patients. There were 206 patients with 158 males and 48 females at average age of 62.21±7.72 years in the layerd manual analstomosis group and 448 patietns with 377 males and 71 females at average age of 62.57±8.42 years in the stapled anastomosis group. We also used Masson trichrome staining to assess the collagen fiber content in the esophagus. Compared with layered manual anastomosis, the incidence of anastomotic leakage was higher in the significant dilatation group than that in the stapled anastomosis group (original cohort: 3.8% vs. 10.7%, P=0.093; propensity score-matched cohort: 1.4% vs. 15.3%, P=0.004). And there was no significant difference in anastomotic leakage b etween layered manual anastomosis and stapled anastomosis in the non-significant dilatation group (original cohort: 4.7% vs. 4.2%, P=0.830; propensity score-matched cohort: 4.8% vs. 4.0%, P=0.206). Moreover, the average collagen fiber area ratio was significantly lower in the significant dilation group than that in the non-significant dilatation group (P=0.045). Conclusion There is a significant reduction in collagen fibers in the proximal esophageal wall tissue of esophageal squamous cell carcinoma patients with a IMPD≥17.9 mm. Intrathoracic layered manual anastomosis effectively reduces postoperative anastomotic leakage in these patients.

Objective: To explore the relationship between adolescent sports participation and aggression, so as to provide a reference basis for sports interventions aimed at reducing adolescent aggression. Methods: The search databases used in the study included China National Knowledge Infrastructure, Vipo, Wanfang, Web of Science, Ebsco, Pro Quest, and PubMed, and the search period was from the construction of the database to October 22, 2023. The search terms for sports participation were "sport" "exercise" "exercise" "physical activity" "physical activity"; the search terms for aggressive behavior were "assault" "aggressive behavior" "aggression"; the search terms for aggressive behavior were "assault" "aggressive behavior" "aggression" "bullying", and "violence", and the above keywords were jointly searched. Foreign language data were searched using Web of Science, Ebsco, Pro Quest, PubMed and supplemented by Google Scholar. The search terms for sports participation were sport, athletics, exercise, train, fitness, physical exercise, physical activity, physical education; and the search terms for aggressive behavior were aggression, bullying, violence, atrocity, fighting, aggressive behavior, physical assault; the above keywords were jointly searched. Statistical analysis was performed using CMA 3.0 software. Results: A total of 20 studies with 80 effect sizes and 9 308 subjects were included. The Metaanalysis showed that adolescent sports participation was moderately negatively correlated with indicators of aggression (r=-0.11), physical aggression (r=-0.14), verbal aggression (r=-0.14), and hostility (r=-0.16), and weakly negatively correlated with indicators of anger (r=-0.08) (P<0.05). Aggressive behavior was influenced by gender, school stage, mode of exercise, and the sports participants region (P<0.05). Conclusions Exercise participation has a positive impact on reducing aggressive behavior in adolescents, and mode of exercise, age, gender, and region are moderating variables in the relationship. Schools can reduce adolescent aggression by developing exercise and physical education interventions.

IgG4-related disease (IgG4-RD) involving the ureter manifested as a ureteral tumor is rare. This paper reports a case of a female patient who was found with a mass at the left ureteropelvic junction for one week during physical examination. Urinary ultrasound and MRI showed a 3 cm mass at the left ureteropelvic junction with hydronephrosis, and the serum level of IgG4 was elevated. B-ultrasonic guided biopsy of the mass was performed. Histopathological findings showed lymphoplasmic infiltration and the ratio of IgG4/IgG positive cells>0.5. We finally diagnosed IgG4-RD and started using glucocorticoid for her treatment. One month later, CT-scan revealed that the tumor became smaller and the serum IgG4 decreased to the normal range.

Ectopic prostate is rare.This paper reports a case of a male patient who was found a mass in the pelvis for 20 days during physical examination.Urinary ultrasound, CT scan and MRI showed a pelvic mass that was about 4 cm×5 cm in size.Serum total prostate specific antigen (tPSA) was 6.09 ng/ml, and free PSA (fPSA) was 1.97 ng/ml. B-ultrasonic guided biopsy of the prostate and the mass was performed. Pathological findings suggest benign prostatic hyperplasia, weakly positive P504S and positive 34βE12. Pelvic mass is the prostate tissue with negative P504S and positive 34βE12. Finally, the ectopic prostate was diagnosed. Although it is rare, ectopic prostate should also be considered as a differential diagnosis of the pelvic tumor.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Objective To analyze the research hotspots and development trends in the pre-hospital emergency care field of stroke in China from 2014 to 2023 using bibliometric method.Methods Retrieve stroke pre-hospital emergency care research articles published in the China National Konwledge Infrastructure(CNKI),WanFang and CQVIP database from 2014 to 2023.Visualize and analyze authors,institutions,and keywords using CiteSpace 5.7.R5 software.Results We included 3,125 articles for analysis.The year 2021 marked the peak of publication activity with 500 articles.The top five authors with the highest number of publications were Guo Wei,Li Dou,Yu Longjuan,Peng Peng,and Zhang Lingjuan,respectively.The Beijing Emergency Center emerged as the institution with the most significant number of publications.Predominant research hotspots encompassed topics such as intravenous thrombolysis,therapeutic outcomes,nerve functions,pathways for emergency nursing care,and green Channel.Current trends are directed towards enhancing the quality of emergency services,optimizing interventional thrombectomy techniques,improving neurological outcomes,and prognostic assessments.Conclusion Over the last decade,there has been a progressive increase in the focus on pre-hospital emergency care research for stroke within China.Future research endeavors should aim at elevating the quality of emergency care,refining thrombectomy approaches,augmenting neurological functional recovery,and improving patient prognoses.