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2.
Am J Pathol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38705384

ABSTRACT

Dyslipolysis of adipocytes has played a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, whether the degree of adipocyte lipolysis relates to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. The visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in caerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study found that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mice AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis could aggravate AP. Genetic blockage of ATGL specifically in adipocytes was able to alleviate the damage to AP. The application of atglistatin could effectively protect against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.

4.
J Orthop Surg Res ; 19(1): 290, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735949

ABSTRACT

BACKGROUND: As an innovative internal fixation system, FNS (femoral neck system) is increasingly being utilized by surgeons for the treatment of femoral neck fractures. At present, there have been numerous finite element analysis experiments studying the immediate stability of FNS and CSS in treating femoral neck fractures. However, there is scarce mechanical analysis available regarding the effects post internal fixation removal. This study aimed to investigate the alterations in mechanical parameters of the proximal femur before and after the removal of FNS (femoral neck system), and to assess potential distinctions in indicators following the extraction of CSS (Cannulated Screws). METHODS: A proximal femur model was reconstructed using finite element numerical techniques. The models for CSS and FNS were formulated utilizing characteristics and parametric definitions. The internal fixation was combined with a normal proximal femur model to simulate the healing state after fracture surgery. Within the framework of static analysis, consistent stress burdens were applied across the entirety of the models. The total deformation and equivalent stress of the proximal femur were recorded before and after the removal of internal fixation. RESULTS: Under the standing condition, the total deformation of the model before and after removing CSS was 0.99 mm and 1.10 mm, respectively, indicating an increase of 12%. The total deformation of the model before and after removing FNS was 0.65 mm and 0.76 mm, respectively, indicating an increase of 17%. The equivalent stress for CSS and FNS were 55.21 MPa and 250.67 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of CSS was 7.76 MPa and 6.11 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of FNS was 9.89 MPa and 8.79 MPa, respectively. CONCLUSIONS: The retention of internal fixation may contribute to improved stability of the proximal femur. However, there still existed risks of stress concentration in internal fixation and stress shielding in the proximal femur. Compared to CSS, the removal of FNS results in larger bone tunnels and insufficient model stability. Further clinical interventions are recommended to address this issue.


Subject(s)
Bone Screws , Femoral Neck Fractures , Finite Element Analysis , Fracture Fixation, Internal , Humans , Biomechanical Phenomena , Femoral Neck Fractures/surgery , Fracture Fixation, Internal/methods , Femur Neck/surgery , Femur Neck/diagnostic imaging , Femur/surgery , Stress, Mechanical , Device Removal/methods
5.
Ann Surg ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38708888

ABSTRACT

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

6.
Front Public Health ; 12: 1349514, 2024.
Article in English | MEDLINE | ID: mdl-38601500

ABSTRACT

Objective: To test the validity and reliability of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) in oncology nurses, the Chinese version was developed. Methods: The Brislin double translation-back translation approach was employed to forward translation, back translation, synthesis, cross-cultural adaptation, and pre-survey, resulting in the first Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON). A convenience sample technique was used to select 350 study participants in Liaoning, Shandong, and Jiangsu, China, who satisfied the inclusion and exclusion criteria, to assess the validity and reliability of the scale. Results: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) had six subscales (perceived threat, perceived benefits, perceived barriers, self-efficacy, cues to action, and personal protective equipment availability and accessibility), including 29 items. The average scale level was 0.931, and the content validity level of the items varied from 0.857 to 1.000. Each Cronbach's α coefficient had an acceptable internal consistency reliability range of 0.806 to 0.902. X2/df = 1.667, RMSEA = 0.044, RMR = 0.018, CFI = 0.959, NFI = 0.905, TLI = 0.954, and IFI = 0.960 were the model fit outcomes in the validation factor analysis. All of the model fit markers fell within reasonable bounds. Conclusion: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) has good reliability and validity and can be used as a tool to assess the influencing factors of chemotherapy exposure for oncology nurses in China.


Subject(s)
Asian People , Humans , Cross-Sectional Studies , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
7.
Ann Intensive Care ; 14(1): 57, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619686

ABSTRACT

BACKGROUND: Plasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients. METHODS: We analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders. RESULTS: A total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00-4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68-1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008). CONCLUSIONS: In HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions. TRIAL REGISTRATION: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020.

8.
Article in English | MEDLINE | ID: mdl-38644529

ABSTRACT

OBJECTIVE: The aim of this study was to develop a web-based dynamic prediction model for postoperative nausea and vomiting (PONV) in patients undergoing gynecologic laparoscopic surgery. METHODS: The patients (N = 647) undergoing gynecologic laparoscopic surgery were included in this observational study. The candidate risk-factors related to PONV were included through literature search. Lasso regression was utilized to screen candidate risk-factors, and the variables with statistical significance were selected in multivariable logistic model building. The web-based dynamic Nomogram was used for model exhibition. Accuracy and validity of the experimental model (EM) were evaluated by generating receiver operating characteristic (ROC) curves and calibration curves. Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model. Decision curve analysis (DCA) was used to evaluate the clinical practicability of the risk prediction model. RESULTS: Ultimately, a total of five predictors including patient-controlled analgesia (odds ratio [OR], 4.78; 95% confidence interval [CI], 1.98-12.44), motion sickness (OR, 4.80; 95% CI, 2.71-8.65), variation of blood pressure (OR, 4.30; 95% CI, 2.41-7.91), pregnancy vomiting history (OR, 2.21; 95% CI, 1.44-3.43), and pain response (OR, 1.64; 95% CI, 1.48-1.83) were selected in model building. Assessment of the model indicates the discriminating power of EM was adequate (ROC-areas under the curve, 93.0%; 95% CI, 90.7%-95.3%). EM showed better accuracy and goodness of fit based on the results of the calibration curve. The DCA curve of EM showed favorable clinical benefits. CONCLUSIONS: This dynamic prediction model can determine the PONV risk in patients undergoing gynecologic laparoscopic surgery.

9.
J Org Chem ; 89(8): 5371-5381, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38551317

ABSTRACT

A facile and eco-friendly photoinduced dehydrogenative amination of quinoxalin-2(1H)-ones with aliphatic amines without any metal, strong oxidant, and photocatalyst has been established for the first time. This reaction proceeding efficiently with air as the sole oxidant at room temperature obtains a wide range of 3-aminoquinoxaline-2(1H)-ones in high yields with excellent functional group tolerance. The mechanistic studies show an interesting involvement of quinoxalin-2(1H)-ones as a photosensitizer, which eliminates the requirement for external photocatalysts.

10.
Surg Innov ; 31(2): 157-166, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38339842

ABSTRACT

BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.


Subject(s)
Ascites , Crohn Disease , Humans , Ascites/complications , Crohn Disease/surgery , Crohn Disease/complications , Pilot Projects , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Drainage , Systemic Inflammatory Response Syndrome/complications
11.
Front Immunol ; 15: 1247382, 2024.
Article in English | MEDLINE | ID: mdl-38343546

ABSTRACT

Purpose: The pathogenesis of renal fibrosis (RF) involves intricate interactions between profibrotic processes and immune responses. This study aimed to explore the potential involvement of the pyroptosis signaling pathway in immune microenvironment regulation within the context of RF. Through comprehensive bioinformatics analysis and experimental validation, we investigated the influence of pyroptosis on the immune landscape in RF. Methods: We obtained RNA-seq datasets from Gene Expression Omnibus (GEO) databases and identified Pyroptosis-Associated Regulators (PARs) through literature reviews. Systematic evaluation of alterations in 27 PARs was performed in RF and normal kidney samples, followed by relevant functional analyses. Unsupervised cluster analysis revealed distinct pyroptosis modification patterns. Using single-sample gene set enrichment analysis (ssGSEA), we examined the correlation between pyroptosis and immune infiltration. Hub regulators were identified via weighted gene coexpression network analysis (WGCNA) and further validated in a single-cell RNA-seq dataset. We also established a unilateral ureteral obstruction-induced RF mouse model to verify the expression of key regulators at the mRNA and protein levels. Results: Our comprehensive analysis revealed altered expression of 19 PARs in RF samples compared to normal samples. Five hub regulators, namely PYCARD, CASP1, AIM2, NOD2, and CASP9, exhibited potential as biomarkers for RF. Based on these regulators, a classifier capable of distinguishing normal samples from RF samples was developed. Furthermore, we identified correlations between immune features and PARs expression, with PYCARD positively associated with regulatory T cells abundance in fibrotic tissues. Unsupervised clustering of RF samples yielded two distinct subtypes (Subtype A and Subtype B), with Subtype B characterized by active immune responses against RF. Subsequent WGCNA analysis identified PYCARD, CASP1, and NOD2 as hub PARs in the pyroptosis modification patterns. Single-cell level validation confirmed PYCARD expression in myofibroblasts, implicating its significance in the stress response of myofibroblasts to injury. In vivo experimental validation further demonstrated elevated PYCARD expression in RF, accompanied by infiltration of Foxp3+ regulatory T cells. Conclusions: Our findings suggest that pyroptosis plays a pivotal role in orchestrating the immune microenvironment of RF. This study provides valuable insights into the pathogenesis of RF and highlights potential targets for future therapeutic interventions.


Subject(s)
Computational Biology , Pyroptosis , Animals , Mice , Cross Reactions , Caspase 1 , Cluster Analysis
12.
J Agric Food Chem ; 72(9): 4658-4668, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38388372

ABSTRACT

Food security is an important issue in the 21st century; preventing and controlling crop diseases and pests are the key to solve this problem. The creation of new pesticides based on natural products is an important and effective method. Herein, coumarins were selected as parent structures, and a series of their derivatives were designed, synthesized, and evaluated for their antiviral activities, fungicidal activities, and insecticidal activities. We found that coumarin derivatives exhibited good to excellent antiviral activities against tobacco mosaic virus (TMV). The antiviral activities of I-1, I-2a, I-4b, II-2c, II-2g, II-3, and II-3b are better than that of ribavirin at 500 µg/mL. Molecular docking research showed that these compounds had a strong interaction with TMV CP. These compounds also showed broad-spectrum fungicidal activities against 14 plant pathogenic fungi. The EC50 values of I-1, I-2a, I-3c, and II-2d are in the range of 1.56-8.65 µg/mL against Rhizoctonia cerealis, Physalospora piricola, Sclerotinia sclerotiorum, and Pyricularia grisea. Most of the compounds also displayed good insecticidal activities against Mythimna separata. Pesticide-likeness analysis showed that these compounds are following pesticide-likeness and have the potential to be developed as pesticide candidates. The present work lays a foundation for the discovery of novel pesticide lead compounds based on coumarin derivatives.


Subject(s)
Fungicides, Industrial , Insecticides , Pesticides , Tobacco Mosaic Virus , Structure-Activity Relationship , Pesticides/pharmacology , Fungicides, Industrial/chemistry , Antiviral Agents/chemistry , Coumarins/chemistry , Molecular Docking Simulation , Insecticides/chemistry , Drug Design
13.
J Crohns Colitis ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38253914

ABSTRACT

BACKGROUND: Azathioprine (AZA) effectively prevents postoperative endoscopic recurrence (ER) in Crohn's disease (CD). However, the efficacy of AZA emerge needs 3 months. Exclusive enteral nutrition (EEN) can maintain remission for CD. The trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. METHODS: Totally, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus a 3-month EEN (AZA+EEN) postoperatively. The primary endpoint was the rate of ER at month 12. Secondary endpoint included the rate of ER at month 3, clinical recurrence (CR), CD activity index (CDAI) scores, fecal calprotectin (FC) and CRP. Quality of life were assessed using Short Form-36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: The patients in the AZA+EEN group exhibited significantly lower rates of ER compared to the AZA group at both months 12 (33.3% [13/39] vs 63.2% [24/38], P=0.009) and months 3 (8.6% [3/35] vs 28.1% [9/32], P=0.037) post-surgery. The rates of CR between the two groups at month-3 and month-12 were similar. The CDAI scores, FC, albumin level and CRP were all comparable between the 2 groups. The quality of life was significantly higher in the AZA group than that of the AZA+EEN group at month 3 but became comparable from month 5 to 12 postoperatively. CONCLUSION: In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted.

14.
J Minim Invasive Gynecol ; 31(4): 285-294, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38237658

ABSTRACT

STUDY OBJECTIVE: This study aimed to explore the relationship between intravenous 5% dextrose infusion during emergence from anesthesia to postoperative nausea and vomiting (PONV) in patients after gynecologic laparoscopic surgery. DESIGN: This was a double-blind randomized controlled trial. Participants were randomized into the experimental group and control group using a computer-generated random number generator. Intervenors and measurers were blinded to group assignments of the study. SETTING: A single academic tertiary medical center. PATIENTS: Patients undergoing gynecologic laparoscopic surgery. INTERVENTIONS: On completion of surgery, participants were randomized into the test group (receive 5% dextrose) and control group (receive Ringer's lactate solution). MEASUREMENTS AND MAIN RESULTS: The primary outcome of the present study was the incidence of PONV. Other outcomes included postoperative rescue analgesic and rescue antiemetic, postoperative pain response, and recovery time of postanesthesia care unit. Baseline characteristics were statistically similar between the 2 groups of participants. There were 49 of 105 patients experienced PONV within 24 hours postoperatively. The overall incidence of PONV within 24 hours postoperatively was not significantly different (45.5% vs 48%; relative risk [RR], 0.95; 95% confidence interval [CI], 0.67-1.37; p = .794). However, fewer patients experienced PONV in the test group than in the control group during 0 to 1 hours (6.0% vs 20.0%; RR, 0.85; 95% CI, 0.73-0.99; p = .024) and 1 to 3 hours (14.5% vs 32.0%; RR, 0.80; 95% CI, 0.64-0.99; p = .033) postoperatively. In addition, recovery time in the postanesthesia care unit was less in the test group (17.07 ± 6.36 vs 22.04 ± 7.33; mean difference, -4.97; 95% CI, -7.62 to -2.32; p <.001) and pain score was lower in the test group during 0 to 0.5 hours postoperatively (2.29 ± 1.74 vs 3.08 ± 1.64; mean difference, -0.79; 95% CI, -1.45 to -0.13; p = .019). CONCLUSION: In patients after gynecologic laparoscopic surgery, postanesthesia 5% dextrose infusion may be useful in improving the early management of PONV and pain response and may warrant further study.


Subject(s)
Anesthesia , Antiemetics , Laparoscopy , Humans , Female , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/etiology , Postoperative Nausea and Vomiting/prevention & control , Laparoscopy/adverse effects , Antiemetics/therapeutic use , Glucose/therapeutic use , Gynecologic Surgical Procedures/adverse effects , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Double-Blind Method
15.
Chem Commun (Camb) ; 60(3): 292-295, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38059581

ABSTRACT

Construction of the pyridine ring is a practical and streamline way to construct a variety of quindoline derivatives. We have developed a novel method for synthesis of quindoline derivatives by means of intramolecular ring-closure reactions of 3-N-methylphenylindoles via an iminium salt intermediate. This practical method has the advantages of a short reaction time, operational simplicity, and nearly quantitative yields; and it can be used for the rapid synthesis of a variety of valuable quindoline derivatives.

16.
Dig Liver Dis ; 56(2): 297-304, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37586905

ABSTRACT

BACKGROUND: Hypertriglyceridemia is a common cause of acute pancreatitis. Pregnant women are at risk of developing hypertriglyceridemia-induced acute pancreatitis (HTG-AP); however, whether pregnancy increases the risk of infected pancreatic necrosis (IPN) is unknown. AIM: We aimed to assess the association between pregnancy and IPN. METHODS: This 10-year retrospective cohort study was conducted at Jinling Hospital. Adult female patients of childbearing age with HTG-AP between January 2013 and September 2022 were screened. Logistic regression analyses were performed to assess the risk factors for IPN. Patients admitted within 7 days were assigned to the training and validation sets to develop a dynamic nomogram for IPN prediction. RESULTS: 489 patients were included, and 144 developed IPN. Logistic regression analyses revealed pregnancy (OR: 2.578 95% CI: 1.474-4.510) as an independent risk factor for IPN. Gestation weeks, ARDS, albumin level, and serum creatinine level were selected as the predictors of the dynamic nomogram for IPN prediction, with good discrimination in the training set (AUC 0.867 95% CI: 0.794-0.940) and validation set (AUC 0.957 95% CI: 0.885-1.000). CONCLUSION: Pregnancy increases the risk of IPN in adult patients of childbearing age with HTG-AP, and the dynamic nomogram may help risk stratification for IPN.


Subject(s)
Hypertriglyceridemia , Pancreatitis, Acute Necrotizing , Pregnancy , Adult , Humans , Female , Pancreatitis, Acute Necrotizing/complications , Acute Disease , Nomograms , Retrospective Studies , Hypertriglyceridemia/complications
17.
Angew Chem Int Ed Engl ; 63(6): e202318344, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38126567

ABSTRACT

Sulfilimines, the aza-variants of sulfoxides, are key structural motifs in natural products, pharmaceuticals, and agrochemicals; and sulfilimine synthesis is therefore important in organic chemistry. However, methods for radical sulfilimination remain elusive, and as a result, the structural diversity of currently available sulfilimines is limited. Herein, we report the first protocol for decarboxylative radical sulfilimination reactions between sulfenamides and N-hydroxyphthalimide esters of primary, secondary, and tertiary alkyl carboxylic acids, which were achieved via a combination of photoredox, copper, and Brønsted base catalysis. This novel protocol provided a wide variety of sulfilimines, in addition to serving as an efficient route for the synthesis of S-alkyl/S-aryl homocysteine sulfilimines and S-(4-methylphenyl) homocysteine sulfoximine. Moreover, it could be used for late-stage introduction of a sulfilimine group into structurally complex molecules, thereby avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. A mechanism involving photocatalytic substrate transformation and copper-mediated C(sp3 )-S bond formation is proposed.

18.
Chem Sci ; 14(46): 13367-13383, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38033906

ABSTRACT

N-Heterocyclic carbenes (NHCs) are unique Lewis basic catalysts that mediate various organic transformations by means of polarity reversal. Although the scope of research on two-electron reactions mediated by NHC catalysts has been expanding, the types of these reactions are limited by the inability of NHCs to engage sp3-electrophiles. However, the revival of photocatalysis has accelerated the development of free-radical chemistry, and combining photoredox catalysis and NHC catalysis to achieve NHC-mediated radical reactions under mild conditions could overcome the above-mentioned limitation. This review summarizes recent advances in combining photoredox and NHC catalysis, focusing on elucidation and exploration of mechanisms, with the aim of identifying challenges and opportunities to develop more types of catalytic models.

19.
PLoS One ; 18(11): e0294779, 2023.
Article in English | MEDLINE | ID: mdl-38011086

ABSTRACT

BACKGROUND: Sepsis is characterized by upregulated lipolysis in adipose tissue and a high blood triglyceride (TG) level. It is still debated whether serum TG level is related to mortality in septic patients. The aim of this study is to investigate the association between serum TG level and mortality in septic patients admitted to the intensive care unit (ICU). METHODS: Data from adult septic patients (≥18 years) admitted to the ICU for the first time were obtained from the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database. The patients' serum TG levels that were measured within the first week after ICU admission were extracted for statistical analysis. The endpoints were 28-day, ICU and in-hospital mortality. RESULTS: A total of 2,782 septic patients were included. Univariate analysis indicated that the relationship between serum TG levels and the risk of mortality was significantly nonlinear. Both the Lowess smoothing technique and restricted cubic spline analyses revealed a U-shaped association between serum TG levels and mortality among septic patients. The lowest mortality rate was associated with a serum TG level of 300-500 mg/dL. Using 300∼500 mg/dL as the reference range, we found that both hypo-TG (<300 mg/dL) and hyper-TG (≥500 mg/dL) were associated with increased mortality. The result was further adjusted by Cox regression with and without the inclusion of some differential covariates. CONCLUSIONS: There was a U-shaped association between serum TG and mortality in septic ICU patients. The optimal concentration of serum TG levels in septic ICU patients is 300-500 mg/dL.


Subject(s)
Sepsis , Shock, Septic , Adult , Humans , Critical Care , Intensive Care Units , Hospital Mortality , Retrospective Studies
20.
Gynecol Oncol ; 178: 8-13, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37734188

ABSTRACT

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.


Subject(s)
Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Aged , Adult , Human Papillomavirus Viruses , Cohort Studies , Prospective Studies , Human papillomavirus 16 , Human papillomavirus 18 , Papillomavirus Infections/drug therapy , Papillomaviridae , Genotype
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