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.

ObjectiveTo explore the differences existing in the auditory mismatch negativity （MMN） amplitude and latency between children with attention deficit hyperactivity disorder （ADHD） and normal children， and to probe into the significance of MMN latency and amplitude for assessing the auditory perception and attention level in ADHD children and normal children. MethodsOn December 1， 2022， a systematic search was performed in PubMed， Embase， Cochrane Library， China National knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform and VIP databases to identify all well qualified literature focusing on MMN of ADHD children， then the valid data relevant to MMN amplitude and latency were extracted. The Newcastle-Ottawa Scale （NOS） was used to assess the quality of the included studies， and Stata 20.0 was employed for Meta-analysis. ResultsA total of 9 qualified studies comparing ADHD children （n=170） against healthy controls （n=159） were finally included. Among the included literature， there were 18 matched pairs of MMN amplitude data and 10 matched pairs of MMN latency data at different recording sites. Meta-analysis denoted that ADHD group resulted in potentials of slightly lower MMN amplitude （WMD=-0.334， 95% CI： -1.426~0.758， P=0.549） and notably longer MMN latency （WMD=14.768， 95% CI： 4.660~24.876， P=0.004） compared to control group， and the Bgger's funnel plot did not reveal any publication bias. ConclusionCompared with healthy controls， ADHD children have longer MMN latency， suggesting that the auditory perception and attention level of ADHD children may be reduced.

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

Asthma is a common chronic airway inflammatory disease, which is characterized by airway stenosis, airway wall thickening and increased mucus secretion followed by reversible airflow restriction.At present, asthma is considered to be a complex and heterogeneous disease, and its pathogenesis remains elusive.There are diverse immune cells involved in the formation of asthma, including T lymphocytes, eosinophils, neutrophils, etc.Due to the continuous renewal of classification and function of T lymphocytes subsets, their role in asthma has attracted more attention.Here, this review aims to summarize the immunological characteristics and roles of different T cell subsets in asthma, and highlight the new findings of T cell subsets in the pathogenesis of severe asthma, leading to provide inspiration and help for the study of the immunology pathogenesis, clinical diagnosis, treatment and prognosis in asthma.

Objective:To investigate the distribution of respiratory pathogens and risk factors of death in patients with pulmonary infection in neurosurgical intensive care unit (NICU).Methods:A total of 87 patients with pulmonary infection in the NICU of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from January 2018 to December 2019 were collected, and the pathogens of their respiratory tract were analyzed to understand the types and distribution of bacteria in the lung infection. Univariate statistical analysis was used to analyze the relationship between the patient′s clinical outcome with age, diabetes, hypertension, renal insufficiency, hypoproteinemia, anemia, chronic respiratory disease, surgery, tracheotomy, and bacterial multi-resistance. Binary logistic regression analysis was used to analyze the influencing factors of death in NICU patients with pulmonary infection.Results:A total of 112 pathogenic bacteria were isolated in this research group, including 83 Gram-negative bacteria (74.11%), 22 Gram-positive bacteria (19.64%), and 7 Fungi (5.25%). Imipenem was highly sensitive to Gram-negative bacteria, vancomycin was highly sensitive to Gram-positive bacteria, and other drugs were highly resistant. 41 patients died (47.13%). Age≥60 ( OR=3.501, 95% CI: 1.152-10.638), renal insufficiency ( OR=3.872, 95% CI: 1.336-11.224), tracheotomy ( OR=0.317, 95% CI: 0.114-0.882), bacteria multi-drug resistance ( OR=3.480, 95% CI: 1.162-10.422) were independent risk factors for death in NICU patients with pulmonary infection. Conclusions:Patients with severe neurological diseases are in critical condition, and there are many patients with pulmonary infection, with poor prognosis and high mortality. Gram-negative bacteria are the most common respiratory pathogens. Carbapenems account for the highest proportion of antibiotics in clinic. Advanced age, renal insufficiency and bacterial multidrug resistance increase the mortality of patients, while early tracheotomy can reduce the mortality of patients.

Objective:To observe the multimodal imaging features of the eyes with acute syphilitic post-polar squamous chorioretinitis (ASPPC) at different stages of disease.Methods:A retrospective case study. From July 2016 to March 2019, 8 patients (11 eyes) of ASPPC patients diagnosed in the ophthalmological examination of Yunnan Second People's Hospital were included in the study. Among them, there were 7 males (10 eyes) and 1 female (1 eye); the average age was 48.7±8.9 years; the average course of disease was 13.24±11.30 months. All patients underwent fundus color photography, infrared photography (IR), FAF, FFA, OCT, OCT angiography (OCTA). According to the stage and characteristics of the disease, the affected eyes were divided into acute phase and absorption phase, with 7 and 4 eyes respectively. We observed the color fundus images of ASPPC, IR, FAF, FFA, OCT, OCTA image characteristics of different disease stages.Results:In the acute phase, the posterior pole subretinal yellow-white squamous lesions, neuroepithelial detachment, and yellow-white exudates were observed in fundus color photography; uneven infrared reflections can be seen in the lesion area by IR; the posterior pole was round or scaly with strong autofluorescence in FAF, the range was larger than the fundus color photography; FFA arteriovenous stage lesions showed fuzzy weak fluorescence, the fluorescence gradually increased with time, the late stage showed a round-shaped strong fluorescence, surrounded by a weak fluorescence ring, and the area with thick exudation was covered by fluorescence; the neuroepithelium of the diseased area was detached, the uniform strong reflection signal can be seen in it by OCT. In the absorption phase, fundus color photography showed the yellow-white scaly lesions under the posterior retina absorption, and the pigment was slightly depleted; IR showed the mottled infrared reflection in the lesion area was significantly reduced compared with the acute phase; FAF showed the posterior spot-like strong autofluorescence, including "leopard spot-like changes" 3 eyes; FFA showed mottled fluorescent staining in the lesion, and no fluorescein leakage or accumulation; OCT showed needle-like protrusions in the RPE layer, and the outer membrane and ellipsoid zone were unclear; OCTA showed weakened choroidal capillary blood flow signal, the signal was missing in some areas.Conclusions:In the acute phase of ASPPC, the posterior pole subretinal shows yellow-white squamous lesions, neuroepithelial detachment, yellow-white exudate, FFA shows late fluorescein leakage in the lesion area; in the absorption period, the fundus shows yellow-white lesions have been absorbed, and FFA shows fluorescence dyed without any leakage. OCT indicates that the RPE, outer membrane and ellipsoid zone are damaged to varying degrees. OCTA indicates that the choroid of the diseased area had weakened blood flow signal.

Objective To analyze the clinical outcome of definitive perineal urethrostomy for the treatment of complex adult anterior urethral strictures.Methods From June 2012 to February 2018,28 patients who underwent the definitive perineal urethrostomy for a complex anterior urethral stricture were retrospectively reviewed.The mean age of the patients was 62.3 (range 34 to 77) years and stricture etiology was lichen sclerosus in 46.4％ (13/28) of the cases,iatrogenic stricture after transurethral resection of the prostate in 35.7％ (10/28),failed hypospadias repair in 10.7％ (3/28),infection 3.6％ (1/28)and idiopathic etiology 3.6％ (1/28).The mean stricture length was 9.6 (range 4.5 to 16.0) cm and the stricture length ＜5 cm in 7.1％ (2/28) of the cases,5-10 cm in 35.7％ (10/28) and ＞ 10 cm in 57.1％ (16/28).0f28 patients 21 (75％) underwent prior urethral dilation,4 (14.3％) underwent direct vision internal urethrotomy (DVIU) and 17 (60.7％) underwent urethroplasty.Among the medical history of interest,hypertension was observed in 17 patients (60.7％),chronic ischemic heart disease in 11 patients (39.3％),diabetes mellitus in 9 patients (32.1％) and chronic obstructive pulmonary disease (COPD) in 9 patients (32.1％).All patients completed the perineal urethrostomy with inverted U-shaped perineal skin flap.The patient was placed in a normal lithotomy position and an inverted U-shaped perineal incision was made.We can get an inverted U-shaped perineal skin flap after dissecting along the bulbospongiosus muscle.The bulbar urethra was opened along the ventral surface and the margins of the spongiosum tissue were closed with perineal skin flap.We analyzed the clinical characteristics of the patients,the outcome of the technique and investigated the satisfaction rates of the patients by outpatient follow-up or telephone interview.Surgical success was defined as functional voiding without the need for further procedures.Results The perioperative complications included 3 cases of urinary tract infection,1 case of bleeding and 1 case of wound dehiscence.Mean follow-up length was 27.2 (range 6.0 to 64.0)months.Of 28 cases 26 (92.9％) were successful and the mean maximum urinary flow rate was 26.5 (range 17.0 to 40.0) ml/s.Postoperatively,2 cases of urethrostomy strictures were found in 2 months and 4 months,respectively.They required periodic outpatient dilation and the younger one was in the waiting list for revision of the perineostomy and the older one refused the revision.Of 28 patients 24 (85.7％) were satisfied with the results obtained with surgery,15 were very satisfied,9 cases satisfied and 4 cases dissatisfied.Conclusions The successful rate of the definitive perineal urethrostomy for the complex adult anterior urethral strictures was high and patients were satisfied with the outcome of the surgery.The definitive perineal urthrostomy is a well-tolerated treatment option for patients with complex anterior urethral strictures,especially for those aged and with extensive comorbidities.

Objective: To study the correlation of lifestyle characteristics with thyroid nodules in a population-based sample of centenarians in Hainan. Methods: The study was based on China Hainan Centenarian Cohort Study (CHCCS) conducted in 18 cities and counties in Hainan province from 2014 to 2016. A group of multidisciplinary team interviewed and examined local centenarians with structured questionnaires and ultrasonography procedures. A total of 918 centenarians were analyzed after excluding those who refused ultrasonographic examinations or had relevant missing data. Thyroids of centenarians were examined by 3-year experienced sonographer, details on lifestyle characteristics and dietary habits were collected by standard procedure. Results: Of the 918 centenarians, 683 (74.4%) had thyroid nodules under the ultrasonography procedures. The prevalence of thyroid nodules in different group of areca nut consumption varied significantly (P<0.05). In multivariate logistic regression model, the results showed female and areca nut intake were independently associated with thyroid nodules in centenarians (P<0.05). Conclusions The modifiable variables including areca nut intake as well as non-modifiable such as gender are independent determinants of thyroid nodules in centenarians. Further studies are warranted to explore and verify these associations in populations with different ranges of age.

Objective To investigate the clinical study of sarcoside combined with tamsulosin in the treatment of type Ⅲ prostatitis. Methods 84 patients with type Ⅲ prostatitis who were treated and diagnosed in Jishuitan Hospital from November 2015 to December 2016 were randomly divided into experimental group and control group according to the time of hospitalization, 42 cases in each group. The control group was treated with tamsulosin hydrochloride sustained-release capsules, and the experimental group was treated with the addition of the new drug. The maximum urinary flow rate and mean urinary flow before and after treatment were recorded, compared and analyzed before and after treatment. Results The maximum urinary flow rate and mean urinary flow rate were increased in both groups after treatment, and there was significant difference between the two groups (P<0.05). The data of the maximum urinary flow rate and the mean urinary flow rate in the experimental group were significantly better than those in the control group. The data of the two groups were statistically significant (P<0.05). In addition, the experimental group after treatment of prostate symptom score was significantly better than the control group score, the two groups of data were significantly different, the data were statistically significant (P<0.05). In addition, the total effective rate of the experimental group was significantly higher than the control group(80.95%vs. 73.81%). The data were statistically significant (P<0.05). Conclusion The clinical efficacy of sorbenaside combined with tamsulosin in the treatment of type Ⅲ prostatitis is better than that of the original treatment. The treatment can improve the patient's urination and prostate symptoms and improve the patient's comfort.

Objective To investigate the clinical effect of antidepressants combined with α-blockers in the treatment of chronic prostatitis.Methods A retrospective analysis of 90 cases of chronic prostatitis treated in our hospital from January 2016 to December 2016 was divided into two groups according to the random number table.The control group was treated with α-blocker Combined with vitamin C treatment, the study group using antidepressants combined with α-blockers treatment.The NIH-CPSI score and SDS score were recorded before and after treatment, and the therapeutic effects were compared between the two groups.Results There were no significant differences in NIH-CPSI scores and SDS scores between the two groups.After treatment, the scores of NIH-CPSI and SDS were significantly better than those before treatment, and the study group was superior to the control(91.1%) was higher than that of the control group(71.1%), the total effective rate of depression(93.3%) was higher than that of the control group(73.3%), and the total effective rate was 91.1%, The difference was statistically significant(P<0.05),comparable.Conclusion Antidepressants combined with α-blockers are effective in the treatment of chronic prostatitis, which is beneficial to the alleviation of clinical symptoms and the improvement of their symptoms.Therefore, it has a good clinical value and worthy of further popularization.