Discovery of Novel Pyridazine Herbicides Targeting Phytoene Desaturase with Scaffold Hopping.

Phytoene desaturase (PDS) is a critical functional enzyme in blocking ζ-carotene biosynthesis and is one of the bleaching herbicide targets. At present, norflurazon (NRF) is the only commercial pyridazine herbicide targeting PDS. Therefore, developing new and diverse pyridazine herbicides targeting PDS is urgently required. In this study, diflufenican (BF) was used as the lead compound, and a scaffold-hopping strategy was employed to design and synthesize some pyridazine derivatives based on the action mode of BF and PDS. The preemergence herbicidal activity tests revealed that compound 6-chloro-N-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenoxy)pyridazine-4-carboxamide (B1) with 2,4-diF substitution in the benzeneamino ring showed 100% inhibition rates against the roots and stems of Echinochloa crus-galli and Portulaca oleracea at 100 µg/mL, superior to the inhibition rates of BF. Meanwhile, compound B1 demonstrated excellent postemergence herbicidal activity against broadleaf weeds, which was similar to that of BF (inhibition rate of 100%) but superior to that of NRF. This indicated that 6-Cl in the pyridazine ring is the key group for postemergence herbicidal activity. In addition, compound B1 could induce downregulation of PDS gene expression, 15-cis-phytoene accumulation, and Y(II) deficiency and prevent photosynthesis. Therefore, B1 can be considered as a promising candidate for developing high-efficiency PDS inhibitors.

Design, Synthesis, and Herbicidal Activity of Novel Tetrahydrophthalimide Derivatives Containing Oxadiazole/Thiadiazole Moieties.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has a high status in the development of new inhibitors. To develop novel and highly effective PPO inhibitors, active substructure linking and bioisosterism replacement strategies were used to design and synthesize novel tetrahydrophthalimide derivatives containing oxadiazole/thiadiazole moieties, and their inhibitory effects on Nicotiana tobacco PPO (NtPPO) and herbicidal activity were evaluated. Among them, compounds B11 (Ki = 9.05 nM) and B20 (Ki = 10.23 nM) showed significantly better inhibitory activity against NtPPO than that against flumiclorac-pentyl (Ki = 46.02 nM). Meanwhile, compounds A20 and B20 were 100% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) at 37.5 g a.i./ha. It was worth observing that compound B11 was more than 90% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) at 18.75 and 9.375 g a.i./ha. It was also safer to rice, maize, and wheat than flumiclorac-pentyl at 150 g a.i./ha. In addition, the molecular docking results showed that compound B11 could stably bind to NtPPO and it had a stronger hydrogen bond with Arg98 (2.9 Å) than that of flumiclorac-pentyl (3.2 Å). This research suggests that compound B11 could be used as a new PPO inhibitor, and it could help control weeds in agricultural production.

Detection of cytotoxins by sandwich-ELISA for discrimination of cobra envenomation and indication of necrotic severity.

Snake envenoming is both a healthcare and socioeconomic problem for developing countries and underserved communities. In Taiwan, clinical management of Naja atra envenomation is a major challenge, since cobra venom-induced symptoms are usually confused with hemorrhagic snakebites and current antivenom treatments do not effectively prevent venom-induced necrosis for which early surgical debridement should be administered. Identification and validation of biomarkers of cobra envenomation is critical for progress in setting a realistic goal for snakebite management in Taiwan. Previously, cytotoxin (CTX) was determined as one of potential biomarker candidates; however, its ability to discriminate cobra envenoming remains to be verified, especially in clinical practice. In this study, we selected a monoclonal single-chain variable fragment (scFv) and a polyclonal antibody to develop a sandwich enzyme-linked immunosorbent assay (ELISA) for CTX detection, which successfully recognized CTX from N. atra venom over that from other snake species. Using this specific assay, the CTX concentration in envenoming mice was shown to remain consistent in about 150 ng/mL during the 2-hour post-injection period. The measured concentration was highly correlated with the size of local necrosis in mouse dorsal skin, which the correlation coefficient is about 0.988. Furthermore, our ELISA method displayed 100 % of specificity and sensitivity in discriminating cobra envenoming among snakebite victims through CTX detection and the level of CTX in victim plasma was ranged from 5.8 to 253.9 ng/mL. Additionally, patients developed tissue necrosis at plasma CTX concentrations higher than 150 ng/mL. Thus, CTX not only serves as a verified biomarker for discrimination of cobra envenoming but also a potential indicator of severity of local necrosis. In this context, detection of CTX may facilitate reliable identification of envenoming species and improve snakebite management in Taiwan.

Immunoprofiling of Equine Plasma against Deinagkistrodon acutus in Taiwan: Key to Understanding Differential Neutralization Potency in Immunized Horses.

Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. Deinagkistrodon acutus is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against D. acutus envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to D. acutus venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against D. acutus venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.

Novel Pyrazole Amides as Potential 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for the development of new herbicides. HPPD inhibitors can hinder photosynthesis and induce weed death with bleaching symptoms. To explore the novel skeleton of HPPD inhibitors, a series of novel pyrazole amide derivatives were synthesized and evaluated for their inhibitory effects on Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activities. Some compounds had excellent inhibitory activities against AtHPPD. Among them, compound B5 displayed top-rank inhibitory activity against AtHPPD with an IC50 value of 0.04 µM, which was obviously superior to that of topramezone (IC50 value of 0.11 µM). Furthermore, compounds B2 and B7 had 100% herbicidal activities in Petri dish assays against Portulaca oleracea and Amaranthus tricolor at 100 µg/mL. In particular, compound B7 not only possessed strong AtHPPD inhibitory activity but also exhibited significant preemergence herbicidal activity. However, compound B7 was completely harmless to soybean, cotton, and wheat. In addition, the molecular docking and microscale thermophoresis measurement experiment verified that compounds can bind well with AtHPPD via π-π interactions. The present work provides a new approach for the rational design of more effective HPPD inhibitors, and pyrazole amides could be used as useful substructures for the development of new HPPD inhibitors and preemergence herbicidal agents.

Development of a Monoclonal scFv against Cytotoxin to Neutralize Cytolytic Activity Induced by Naja atra Venom on Myoblast C2C12 Cells.

The Taiwanese cobra, Naja atra, is a clinically significant species of snake observed in the wild in Taiwan. Victims bitten by N. atra usually experience severe pain and local tissue necrosis. Although antivenom is available for treatment of cobra envenomation, its neutralization potency against cobra-induced necrosis is weak, with more than 60% of cobra envenoming patients developing tissue necrosis after antivenom administration. The present study found that cytotoxin (CTX) is a key component of N. atra venom responsible for cytotoxicity against myoblast cells. Anti-CTX IgY was generated in hens, and the spleens of these hens were used to construct libraries for the development of single chain variable fragments (scFv). Two anti-CTX scFv, S1 and 2S7, were selected using phage display technology and biopanning. Both polyclonal IgY and monoclonal scFv S1 reacted specifically with CTX in cobra venom. In a cell model assay, the CTX-induced cytolytic effect was inhibited only by monoclonal scFv S1, not by polyclonal IgY. Moreover, the neutralization potency of scFv S1 was about 3.8 mg/mg, approximately three times higher than that of conventional freeze-dried neurotoxic antivenom (FNAV). Collectively, these results suggest that scFv S1 can effectively neutralize CTX-induced cytotoxicity and, when combined with currently available antivenom, can improve the potency of the latter, thereby preventing tissue damage induced by cobra envenoming.

Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A2 activity with varespladib.

Protobothrops mucrosquamatus, also known as the brown spotted pit viper or Taiwanese habu, is a medically significant venomous snake in Taiwan, especially in the northern area. To more fully understand the proteome profile of P. mucrosquamatus, we characterized its venom composition using a bottom-up proteomic approach. Whole venom components were fractionated by RP-HPLC and then analyzed by SDS-PAGE. Each protein band in gels was excised and subjected to protein identification by LC-MS/MS. A subsequent proteomic analysis revealed the presence of 61 distinct proteins belonging to 19 families in P. mucrosquamatus venom. Snake venom metalloproteinase (SVMP; 29.4%), C-type lectin (CLEC; 21.1%), snake venom serine protease (SVSP; 17.6%) and phospholipase A2 (PLA2; 15.9%) were the most abundant protein families, whereas several low-abundance proteins, categorized into eight protein families, were demonstrated in P. mucrosquamatus venom for the first time. Because PLA2 is known to make a major contribution to venom lethality, we evaluated whether the known PLA2 inhibitor, varespladib, was capable of preventing the toxic effects of P. mucrosquamatus venom. This small-molecule drug demonstrated the ability to inhibit PLA2 activity in vitro (IC50 = 101.3 nM). It also blunted lethality in vivo, prolonging survival following venom injection in a mouse model, but it showed limited potency against venom-induced local hemorrhage in this model. Our findings provide essential biological and pathophysiological insights into the composition of P. mucrosquamatus venom and suggest PLA2 inhibition as an adjunctive or alternative therapeutic strategy in the clinical management of P. mucrosquamatus envenoming in emergency medicine. SIGNIFICANCE: P. mucrosquamatus envenomation is a significant medical concern in Taiwan, especially in the northern region. Although antivenom is commonly used for rescuing P. mucrosquamatus envenoming, severe clinical events still occur, with more than 20% of cases requiring surgical intervention. Small-molecule therapy offers several advantages as a potential adjunctive, or even alternative, to antivenom treatment, such as heat stability, low antigenicity and ease of administration, among others. A deeper understanding of the venom proteome of P. mucrosquamatus would aid in the discovery of small-molecule drugs that could be repurposed to target specific venom proteins. Here, we applied a bottom-up proteomic approach to characterize the protein profile of P. mucrosquamatus venom. Varespladib, a small-molecule drug used to treat inflammatory disease, was repurposed to inhibit the toxicity of P. mucrosquamatus venom, and was shown to reduce the lethal effects of P. mucrosquamatus envenomation in a rodent model. Varespladib might be used as a first-aid therapeutic against P. mucrosquamatus envenoming in the pre-referral period and/or as an adjunctive agent administered together with anti-P. mucrosquamatus antivenom.

Abdominal Tuberculosis Managed Surgically in the Late Phase: A Case Report.

About 1-5 % of cases of tuberculosis (TB) have uncommon abdominal conditions, and affect primarily young adults. The clinical diagnosis is challenging and often delayed due to the symptoms being non-specific and may be confused with other bowel diseases, therefore resulting in significant morbidity and mortality. A 27-year-old man was brought to our emergency department with the complaints a fever and abdominal pain. According to the chest X-ray findings taken 24 hours previously, pulmonary TB was suspected. Abdominal TB associated intestinal obstruction, ascites and lymphadenopathy were found by computed tomography and exploratory laparotomy. He was treated surgically by segmental resection, however passed away due to severe bleeding caused by the recurrence of perforation of the small intestine and sepsis. This case of systemic TB highlights the difficulties in diagnosis and treatment in time. The early diagnosis and timely treatment are both necessary to manage the disease successfully.

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models.

Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan.

Disease Burden of Esophageal Cancer Attributable to Smoking from 1990 to 2019 in China / 中山大学学报(医学科学版)

ObjectiveTo analyze the trends in the disease burden of esophageal cancer attributed to smoking in China from 1990 to 2019. MethodsUsing the Joinpoint 4.9.1.0 software， based on the Global Burden of Disease Study 2019 data， we examined the mortality， Disability-Adjusted Life Years （DALY） data， and death rates of esophageal cancer attributed to smoking in China from 1990 to 2019， along with national population data. The trends in disease burden was described and the age-period-cohort model was employed to analyze the effects of age， period， and cohort on the trends in disease burden due to smoking. ResultsJoinpoint analysis indicated that the age-standardized mortality rate （ASMR） and DALY rate attributable to smoking showed an average annual percent change （AAPC） of -1.42% and -1.72%， respectively. For females， the AAPC values for ASMR and DALY rate were -3.26% and -3.70%， respectively， while for males， these were -1.28% and -1.54%， respectively. The disease burden by age attributable to smoking showed a general declining trend across all age groups in mortality and DALY rates. The disease burden from smoking， measured by age， displayed a consistent downward trend in both mortality and DALY rates across all age groups. The 40-44 age group saw the sharpest decline， with Annual Average Percent Changes （AAPC） of -3.05% for mortality and -3.04% for DALY rates. This was closely followed by the 45-49 age group， which experienced AAPC values of -2.73% and -2.72%， respectively. Analysis using the age-period-cohort model showed that the impact of age on mortality and DALY rates due to smoking initially increases with age before subsequently decreasing. The period effect revealed a general increase in the mortality rate from smoking in China， except for a dip between 2005 and 2010； otherwise， the trend was upward over time. The DALY rate demonstrated variability across different periods. The cohort effect indicated a decrease in both mortality and DALY rates due to smoking as successive birth cohorts progressed. ConclusionsOur study reveals that the disease burden of esophageal cancer attributed to smoking factors exhibits gender differences and shows an overall declining trend over time. Efforts should be intensified to enhance health education for men， particularly focusing on smoking cessation education for smokers aged 35-39， in order to improve the overall level of primary prevention of esophageal cancer.

Investigation and study of factors related to NCD health management of basic public health services in Chongqing and Guizhou Province / 重庆医学

Objective To analyze the health management situation of non-communicable chronic disease(NCD)in Chongqing City and Guizhou Province and its influencing factors.Methods A stratified random sampling method was used to select 16 representative primary medical and health institutions from Chongqing City and Guizhou Province as the research sites,and the data were collected through the combination method of qualitative and quantitative research.Results A total of 760 patients with NCD were surveyed,and the awareness rate,utilization rate and satisfaction rate of the NCD health management program all exceeded 84.2％,while the awareness rate,utilization rate and satisfaction rate of follow-up and categorical intervention were the lowest.The awareness rate of hypertension physical examination in the patients with＜60 years old was lower than that in the patients with 60-＜70 years old(OR=4.28,95％CI:1.43-12.81)and the pa-tients with ≥70 year sold(OR=3.16,95％CI:1.12-8.91);the utilization rate of diabetes screening in the patients with＜60 years-old was lower than that in the patients with ≥70 years old(OR=2.70,95％CI:1.08-6.76)and the awareness rate of hypertension physical examination was lower than that of the patients with 60-＜70 years old(OR=4.24,95％CI:1.01-17.75);the awareness rate of hypertension physical ex-amination in the patients in Chongqing City was higher than that in Guizhou Province(OR=0.15,95％CI:0.04-0.54)and the utilization situation was better than that in Guizhou Province(OR=0.13,95％CI:0.05-0.34).Conclusion The overall situation of NCD management services in Chongqing City and Guizhou Province is good,but the service quality of follow-up and classified intervention projects needs to be further improved.

Correlation between plasma NT-proBNP level and postoperative outcomes in elderly and critically ill patients with hip fractures / 临床麻醉学杂志

Objective To investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP＞1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P＜0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P＜0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.

Analysis on the homogeneity of clinical basic skills teaching based on OSCE exam scores / 沈阳医学院学报

Objective:To identify and improve the weakness in different clinical practice teaching hospital,and enhance the quality of practical teaching.Methods:A total of 291 trainees majoring in clinical medicine in grade 2016 in a medical college in Shenyang who practiced in different clinical teaching hospitals and participated in the objective structured clinical examination(OSCE)were enrolled.The OSCE scores was analyzed with one way ANOVA and Kruskal-Wallis statistic methods to identify the weakness in clinical practice teaching and improve the teaching quality.Results:In the standardized patient consultation and physical examination results,the passing rate and average score of H hospital was the lowest.The average score of trainees in H hospital was statistically significant compared to that in A,B,F,G,K,and L hospitals(P＜0.01).In terms of skill operation scores,H hospital had the lowest pass rate and average score.The average score of interns in H hospital was statistically significant compared to that in A,D,E,F,G,I,J,K hospitals(P＜0.01).In the interpretation of auxiliary examination results,the passing rate and average score of H hospital was the lowest.The average score of interns in A and H hospital was significantly different from that of B and J hospitals(P＜0.01).Conclusions:There are great differences in the practice effect of students in different clinical teaching hospitals.Medical colleges and universities should strengthen the management of clinical teaching hospitals to ensure the homogeneity of clinical practice teaching quality.

Curative effect of unilateral thyroid lobectomy by different approaches in the treatment of papillary thyroid microcarcinoma / 中华内分泌外科杂志

Objective:To compare the clinical effects of different approaches of unilateral thyroid lobectomy in the treatment of papillary thyroid microcarcinoma (PTMC) .Methods:From Jun. 2019 to Jun. 2022, 70 patients with PTMC from Thyroid and Breast Surgery Department of Taihe Hospital and Dongfeng General Hospital were selected for prospective study. They were divided into transoral group with 35 cases according to random number table method. Trans-oral endoscopic thyroidectomy (TOET) was adopted in 11 males and 24 females, aging (40.71±5.09) years old, ranging from 23 to 60 years old; 35 cases in the trans-axillary group, using trans-axillary approach Endoscopic thyroidectomy by areola approach (ETAA) including 13 males and 22 females, aging (40.25±5.06) years old, ranging from 24 to 59 years old. Perioperative indicators, inflammatory factors, and stress indicators were recorded in the two groups. The level and complications were followed up for 3 months to evaluate the aesthetics of surgical incisions. The comparison of measurement data between groups was performed by independent t test, and the comparison of count data was conducted by χ2 test. Results:The number of lymph nodes dissected and intraoperative blood loss in the oral cavity group were significantly better than those in the axillary group [ (8.71±0.93) vs (6.85±0.82), (23.05±3.51) ml vs (26.14±3.96) ml] ( t=8.88, 3.46, P<0.05) ; The first day after operation, serum norepinephrine (NE) and cortisol (Cor) in the oral cavity group were significantly lower than those in the axillary group [ (275.31±30.41) ng/L vs (300.22±33.25) ng/L, (180.25±19.75) nmol/L vs (205.36±22.41) nmol/L] ( t=3.27, 4.97, P<0.05) ; The first day after operation, the levels of serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the oral cavity group were significantly lower than those in the axillary group [ (7.05±0.86) mg/L vs (8.74±1.02) mg/L, (4.33±0.62) pg/L vs (6.45±0.81) pg/L] ( t=7.49, 12.30, P<0.05) ; there was no significant difference in the incidence of complications between the groups ( P>0.05) ; Three months postoperatively, the aesthetics of the incision in the oral cavity group (94.29%) was significantly higher than that in the axillary group (77.14%) ( χ2=4.20, P<0.05) . Conclusion:When unilateral thyroid lobectomy is performed for papillary thyroid microcarcinoma, the transoral vestibular approach is less invasive than the transaxillary approach, and the effect of lymph node dissection is better, which is beneficial to reduce the surgical stress response of patients, and the aesthetics of the surgical incision are higher.

Status quo and disease burden of occupational pneumoconiosis in Qinghai Province from 2015 to 2019 / 环境与职业医学

Background Occupational pneumoconiosis is the most common occupational disease in Qinghai Province and China. From the perspective of public health, it is important to assess the disease burden using disability-adjusted life years (DALY) and economic losses. Objective To evaluate the disease burden of occupational pneumoconiosis in Qinghai Province, and to provide a basis for the formulation and implementation of relevant prevention and control strategies. Methods Based on the registered data, a database of occupational pneumoconiosis cases confirmed and reported in Qinghai Province was established. The survival status and death dateof occupational pneumoconiosis patients from 2015 to 2019 were confirmed by on-site visit, telephone survey, matching search of Death Information Registration and Management System, and consulting other departments. The life loss due to occupational pneumoconiosis from 2015 to 2019 was assessed using DALY as an indicator and data from the Global Burden of Disease 2019 (GBD 2019) study. Inpatients with officially diagnosed occupational pneumoconiosis from a hospital in Qinghai Province in 2019 were selected as study subjects, the direct economic loss was evaluated with hospitalization expenses, and the indirect economic loss due to occupational pneumoconiosis in Qinghai Province in 2019 was calculated by human capital approach. Results From 2015 to 2019, 505 new cases of occupational pneumoconiosis were reported in Qinghai Province, and there were 348 death cases. Prevalent cases and years lost due to disability (YLD) due to occupational pneumoconiosis were increased, while DALY and years of life lost (YLL) due to occupational pneumoconiosis decreased firstly and then increased. In each year, there were 87% or more of the DALY, YLL, or YLD attributed to silicosis and coal workers' pneumoconiosis. In 2019, the occupational pneumoconiosis-associated DALY was 2173.55 person years. The total hospitalization expense incurred by 42 inpatients with occupational pneumoconiosis was 1256345.19 yuan. The total hospitalization expense and average daily cost of the inpatients with stageⅡand Ⅲ pneumoconiosis were higher than that of the inpatients with stageⅠ (P<0.05), and the hospitalization expense was higher in the ≥60 years age group than in the <60 years age group (P<0.05). In 2019, the indirect economic burden incurred by occupational pneumoconiosis in Qinghai Province was 44108581.65 yuan, and accounted for 0.15‰ of the gross domestic product (GDP) of the province. Conclusion The disease burden associated with occupational pneumoconiosis in Qinghai Province are outstanding. Silicosis and coal workers' pneumoconiosis are the key contributors. Targeted intervention measures including dust hazard control, enterprise management, follow-up and rehabilitation management of pneumoconiosis should be taken to prevent and control the occurrence and progression of pneumoconiosis and alleviate disease burden of pneumoconiosis.

Characteristics and implications of curriculum for PHD students of health service management in the world / 中华医学教育探索杂志

Five universities with health policy and management ranked top level worldwide, including Harvard University, John Hopkins University, Stanford University, University of North Carolina at Chapel Hill and National University of Singapore were selected in our study. From above universities, we found that the curriculum of PHD students was focused on research concentration, methodology courses, and numerous elective courses. Hence, in China, the curriculum of PHD students should be improved with emphasis on course studying, management courses and highlighting curriculum content according to research area to enhance the quality of doctoral education.

The value of combined detection of HbA2 and HbF for the screening of thalassemia among individuals of childbearing ages / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region.@*METHODS@#Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves.@*RESULTS@#4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively.@*CONCLUSION@#HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.

Increased risk of pyogenic liver abscess in patients with alcohol intoxication: A population-based retrospective cohort study.

We designed a population-based retrospective cohort study to investigate the association between the event of alcohol intoxication and the risk of pyogenic liver abscess. The present study enrolled 245,076 patients with a history of alcohol intoxication from 2000 to 2010 and matched each of them with four comparison patients, with similar mean age and sex ratios. We determined the cumulative incidences and adjusted hazard ratios (aHRs) of liver abscess. A significant association was observed between alcohol intoxication and liver abscess. The incidence density rate of liver abscess was 3.47-fold greater in the alcohol intoxication (AI) cohort than in the non-AI cohort (12.2 vs. 3.43 per 10,000 person-years), with an adjusted HR (aHR) of 2.64 (95% CI = 2.26 to 3.08). This population-based study positively associated the event of alcohol intoxication with increased risk of liver abscess. Our findings warrant further large-scale and in-depth investigations in this area.

One-year follow-up results of atrial fibrillation patients who undergoing transcatheter aortic valve implantation / 中华心血管病杂志

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.

Factors relating to bone mineral density in young and middle-aged patients with ankylosing spondylitis / 中华医学杂志(英文版)

BACKGROUND@#Ankylosing spondylitis (AS) is a common chronic progressive rheumatic disease. The aim of this study was to explore factors influencing abnormal bone mineral density (BMD) in young and middle-aged patients with AS.@*METHODS@#From July 2014 to August 2018, hospitalized patients with AS and health examinees in the health examination center of our clinics, ranging in age from 20 to 50 years, were monitored. The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption. The BMDs of AS patients were compared with respect to age, course of disease, iritis, smoking habits, sex, height, weight, body mass index (BMI), medication use, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet volume, platelet count, uric acid (UA), alkaline phosphatase (AKP), and calcium ion levels. Single-nucleotide polymorphisms (SNPs) related to BMD were screened using genome-wide association analysis.@*RESULTS@#There was no statistical difference in the proportion of abnormal bone masses between the different body parts. The BMD of all bones in AS patients was lower than that in healthy controls (P < 0.05). Additionally, BMD was correlated with serum calcium and CRP in AS patients (P < 0.05), but not with age, platelet volume, platelet count, ESR, UA, AKP, height, weight, and BMI. The incidence of abnormal bone mass in AS patients was correlated with sex (P < 0.05), but not with medication use, iritis, or smoking. BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease, but BMD of the femoral neck correlated linearly with the course of the disease (P < 0.05). BMD was correlated with multiple SNPs in patients with AS. Lumbar BMD was correlated with rs7025373 and rs7848078. Femoral head BMD was correlated with 3:102157365, 3:102157417, rs1252202, rs1681355, rs3891857, rs7842614, and rs9870734, suggesting that genetic factors play a role in BMD in patients with AS.@*CONCLUSIONS@#The proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age. The factors related to BMD in patients with AS are gender, CRP, and blood calcium. The BMD of the femoral neck of AS patients decreases with the course of the disease, but BMD of the lumbar spine is not related to the course of the disease. BMD in AS patients is associated with multiple SNPs.