Comprehensive analysis of risk factors for flap necrosis in free flap reconstruction of postoperative tissue defects in oral and maxillofacial tumors.

Free flap reconstruction for postoperative tissue defects in oral and maxillofacial tumors is a critical component of reconstructive surgery. Identifying risk factors for flap necrosis is essential for improving surgical outcomes and patient quality of life. A retrospective study was conducted on patients who underwent free flap reconstruction between January 2020 and December 2023. Patients were included if they had comprehensive medical records and at least a six-month follow-up. We excluded those with a history of flap necrosis, uncontrolled systemic diseases, non-adherence to postoperative care, or concurrent malignancy treatments. Data on demographics, comorbidities, flap characteristics, and operative details were collected and analyzed using univariate analysis and logistic regression tests. Univariate analysis did not find a significant correlation between flap necrosis and factors such as hyperlipidemia, lymph node metastasis, or flap type. However, diabetes mellitus, oral infections, and albumin levels below 35 g/L were significantly associated with flap necrosis. Multivariate logistic regression showed diabetes mellitus increased the odds of flap necrosis by approximately ninefold, and oral infection increased it by over tenfold. Diabetes mellitus, oral infection, and low albumin levels are significant risk factors for flap necrosis in free flap reconstruction after oral and maxillofacial surgery. Prompt identification and management of these factors are crucial to mitigate the risk of flap necrosis.

The Economic Burden of Brucellosis Care in China: Socioeconomic Status Inequality.

The economic burden of brucellosis care on patients can lead to significant financial strain, despite partial coverage by medical insurance. However, there is limited research on the out-of-pocket costs faced by brucellosis patients. Therefore, our study aimed to investigate the costs and out-of-pocket expenses of brucellosis care, specifically examining the varying socioeconomic status of patients in Xinjiang, China. We collected cost and demographic data from 563 respondents and their hospital bills and employed latent variable analysis to assess socioeconomic status. The majority of patients belonged to the middle and lower socioeconomic status categories (85.97%), and they were primarily farmers and herders (82.77%). The median direct cost per brucellosis episode was USD 688.65, with out-of-pocket expenses amounting to USD 391.44. These costs exceeded both the 2020 Xinjiang and national per capita health expenditures (USD 233.66 and USD 267.21, respectively). Notably, the overall medical reimbursement rate was 48.60%, and for outpatient costs, it was merely 12.82%. Despite higher out-of-pocket costs among high socioeconomic status patients, the percentage of income spent was higher (37.23%) for patients in the lower socioeconomic status group compared to other groups (16.25% and 12.96%). In conclusion, our findings highlight that brucellosis patients are predominantly from the middle and lower socioeconomic status, with high out-of-pocket expenses placing them under significant financial pressure. Moreover, there is notable inequity in economic consequences across different socioeconomic status groups. These results call for policy interventions aimed at reducing brucellosis-related poverty and promoting equitable access to care.

[Causal relationship between obesity and male infertility: A two-sample Mendelian randomization study].

OBJECTIVE: To clarify the causal relationship between obesity and male infertility through Mendelian randomization (MR) study. METHODS: We assessed the causal effect of genetically predicted body mass index (BMI) on the risk of male infertility via a two-sample MR analysis, with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans. In the univariable MR (UVMR) analysis of the causal relationship, we mainly used inverse variance weighting (IVW), with MR-Egger regression and weighted median filtering as the supplementary methods. Sensitivity analyses including the Cochran's Q test, Egger intercept test, MR-PRESSO, leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results. To evaluate the direct causal effects of BMI on MI risk, multivariable MR (MVMR) was performed. RESULTS: UVMR indicated a causal relationship between genetically predicted BMI and an increased risk of male infertility (OR: 1.237, 95% CI: 1.090－1.404, P = 0.001). Sensitivity analysis revealed little evidence of bias in the current study (P> 0.05). With such risk factors as type 2 diabetes, alcohol consumption and smoking adjusted, MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility (P<0.05). CONCLUSION: Genetically predicted BMI may be associated with an increased risk of male infertility. Further studies are expected to explore the underlying mechanisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Synthesis of 6/5/3-Fused Tricyclic Scaffolds via Multistep Cascade Cyclization of α-Aryl Vinylsulfoniums with para-Quinamines and para-Quinols.

Herein, we present a straightforward approach to access hydroindoline-5-one-based 6/5/3-fused polycyclic ring structures through multistep cascade reactions involving α-aryl vinylsulfoniums and para-quinamines. The reactions proceed smoothly under mild conditions to deliver the desired products in generally good isolated yields. This protocol is also applicable to the cascade cycloaddition reactions of α-aryl vinylsulfoniums and para-quinols, effectively generating complex tricyclic scaffolds. In addition, the scale-up synthesis and further derivatizations demonstrate the potential synthetic application of the protocol.

Palladium-Catalyzed Cycloaddition Reactions of π-Allylpalladium 1,4-Dipoles with 1,3,5-Triazinanes: Access to Hexahydropyrimidines, 1,3-Oxazinanes, and 1,5-Diazocanes.

Palladium-catalyzed decarboxylation of 5-methylene-1,3-oxazinan-2-ones and 5-methylene-1,3-dioxan-2-ones to generate aza-π-allylpalladium and oxa-π-allylpalladium 1,4-dipoles for [4 + 2] cycloaddition reaction with 1,3,5-triazinanes was developed, affording a wide range of hexahydropyrimidine and 1,3-oxazinane derivatives in good to excellent yields (up to 99%). The acyclic sulfonamido-substituted allylic carbonates as aza-π-allylpalladium 1,4-dipole precursors also apply to the developed synthesized strategy, achieving the synthesis of hexahydropyrimidines. Moreover, the in situ-generated aza-π-allylpalladium 1,4-dipoles undergoing dimeric [4 + 4] cycloaddition were also demonstrated by the construction of 1,5-diazocane derivatives.

Recent Advances in the Domino Annulation Reaction of Quinone Imines.

Quinone imines are important derivatives of quinones with a wide range of applications in organic synthesis and the pharmaceutical industry. The attack of nucleophilic reagents on quinone imines tends to lead to aromatization of the quinone skeleton, resulting in both the high reactivity and the unique reactivity of quinone imines. The extreme value of quinone imines in the construction of nitrogen- or oxygen-containing heterocycles has attracted widespread attention, and remarkable advances have been reported recently. This review provides an overview of the application of quinone imines in the synthesis of cyclic compounds via the domino annulation reaction.

[Spatial and Temporal Distribution Characteristics of Ozone Concentration and Health Benefit Assessment in the Beijing-Tianjin-Hebei Region from 2015 to 2020].

To evaluate the spatial and temporal distribution characteristics of ambient ozone (O3) in the Beijing-Tianjin-Hebei (BTH) Region, the land use regression (LUR) model and random forest (RF) model were used to simulate the ambient O3 concentration from 2015 to 2020. Meanwhile, all-cause, cardiovascular, and respiratory mortalities as well as economic losses attributed to O3 were also estimated. The results showed that upward trends with fluctuation were observed for ambient O3 concentration, mortalities, and economic losses attributable to O3 exposure in the BTH Region from 2015 to 2020. The areas with high O3 concentration and great changes were concentrated in the central and southwestern regions, whereas the concentration in the northern region was low, and the change degree was small. The spatial distribution of the mortalities was also consistent with the spatial distribution of O3 concentration. From 2015 to 2020, the economic losses regarding all-cause mortality and cardiovascular mortality increased in 13 cities of the BTH Region, whereas the economic losses of respiratory mortality decreased in 4 cities in the BTH Region. The results indicated that the priority areas for O3 control were not uniform. Specifically, Beijing, Tianjin, Hengshui, and Xingtai were vital areas for O3 pollution control in the BTH Region. Differentiated control measures should be adopted based on the characteristics of these target areas to decline O3 concentration and reduce health impacts and economic losses associated with O3 exposure.

Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines.

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines.

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

Thiol-Triggered Tandem Dearomative Michael Addition/Intramolecular Henry Reaction of 2-Nitrobenzofurans: Access to Sulfur-Containing Polyheterocyclic Compounds.

An efficient dearomative cyclization of 2-nitrobenzofurans via a thiol-triggered tandem Michael addition/intramolecular Henry reaction has been developed. A range of thiochromeno[3,2-b]benzofuran-11-ols and tetrahydrothieno[3,2-b]benzofuran-3-ols could be obtained in up to 99% yield and up to >20:1 dr. The valuable thiochromone fused benzofurans could be prepared with the reaction of 2-nitrobenzofurans and 2-mercaptobenzaldehyde via the tandem dearomative Michael addition/intramolecular Henry reaction/rearomatization/oxidative dehydrogenation process in a one-pot two-step operation. A mechanism for the reaction was tentatively proposed.

Cu-Catalyzed Direct Asymmetric Mannich Reaction of 2-Alkylazaarenes and Isatin-Derived Ketimines.

The first direct catalytic asymmetric Mannich reaction of 2-alkylazaarenes and ketimines was realized with a chiral Cu-bis(oxazoline) complex as the catalyst. The asymmetric addition of 2-alkylpyridines to isatin-derived ketimines proceeded smoothly to afford α,ß-functionalized 2-substituted pyridines bearing 3-amino-3,3-disubstituted oxindole motifs with excellent results (≤99% yield, 99:1 dr, and 98% ee). The catalytic system was also extended to 2-alkylbenzothiazoles as nucleophiles for the asymmetric Mannich reaction of ketimines.

Palladium-Catalyzed Ligand-Directed Divergent Decarboxylative Cycloadditions of Vinyloxazolidine-2,4-diones with 1,3,5-Triazinanes.

This study demonstrates a highly efficient regiodivergent ligand-controlled palladium-catalyzed cycloaddition reaction of vinyloxazolidine-2,4-diones with 1,3,5-triazinanes. In the presence of a diphosphine ligand, the reaction proceeds via a (5+2) cycloaddition pathway to afford 1,3-diazepin-4-ones in excellent yields, while using a monophosphine ligand, the reaction proceeds smoothly via a (3+2) cycloaddition pathway to give imidazolidin-4-ones in good yields.

Incidence and warning signs for complications of human brucellosis: a multi-center observational study from China.

BACKGROUND: Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients. METHODS: A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model evaluation. RESULTS: A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5-58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval (CI) 1.906-8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95% CI 1.176-2.384), arthralgia (OR = 3.197, 95% CI 1.986-5.148), eye bulging pain (OR = 3.482, 95% CI 1.349-8.988), C-reactive protein (CRP) > 10 mg/L (OR = 1.910, 95% CI 1.310-2.784) and erythrocyte sedimentation rate (ESR) elevation (OR = 1.663, 95% CI 1.145-2.415). The optimal cutoff value in ROC analysis was > 5.4 mg/L for CRP (sensitivity 73.4% and specificity 51.9%) and > 25 mm/h for ESR (sensitivity 47.9% and specificity 71.1%). CONCLUSIONS: More than 50% of patients with brucellosis experienced complications. Factors such as diagnostic delay, underlying disease, arthralgia, eye pain, and elevated levels of CRP and ESR were identified as significant markers for the development of complications. Therefore, patients presenting with these conditions should be closely monitored for potential complications, regardless of their culture results and standard tube agglutination test titers.

Sesquiterpenes from Wikstroemia lungtzeensis with anti-neuroinflammatory effects.

An anti-neuroinflammatory activities-guided phytochemical research of Wikstroemia lungtzeensis was performed for the first time. Three undescribed carotane-type sesquiterpenes, excoecafolinols C-E (1-3), and nine known sesquiterpene derivatives were isolated from the effective ethyl acetate extract of W. lungtzeensis. Their structures were determined based on multiple spectroscopic techniques and electronic circular dichroism (ECD) spectra. Furthermore, the anti-neuroinflammatory activities of the identified compounds were evaluated in lipopolysaccharide-stimulated BV-2 cells. Among them, six components (1, 2, 4, 7, 11, 12) exhibited significant inhibitory effects on nitric oxide (NO) production, with IC50 values ranging from 10.48 to 49.41 µM (positive control minocycline, IC50 53.20 µM). Carotane-type sesquiterpenes (1, 2, 4) with high content and significant inhibitory effects, are considered to be major active ingredients of W. lungtzeensis, which might serve as potential therapeutic agents for neurodegenerative diseases.

Progress in Catalytic Asymmetric Reactions with 7-Azaindoline as the Directing Group.

α-Substituted-7-azaindoline amides and α,ß-unsaturated 7-azaindoline amides have emerged as new versatile synthons for various metal-catalyzed and organic-catalyzed asymmetric reactions, which have attracted much attention from chemists. In this review, the progress of research on 7-azaindoline amides in the asymmetric aldol reaction, the Mannich reaction, the conjugate addition, the 1,3-dipole cycloaddition, the Michael/aldol cascade reaction, aminomethylation and the Michael addition-initiated ring-closure reaction is discussed. The α-substituted-7-azaindoline amides, as nucleophiles, are classified according to the type of α-substituted group, whereas the α,ß-unsaturated 7-azaindoline amides, as electrophiles, are classified according to the type of reaction.

A New Reaction Mode of 3-Halooxindoles: Acting as C-C-O Three-Atom Components for (3+3) Cycloaddition to Access Indolenine-Fused 2H-1,4-Oxathiines.

Herein, we report an unprecedented implementation of 3-halooxindoles as C-C-O three-atom components for (3+3) cycloaddition with pyridinium 1,4-zwitterionic thiolates, affording structurally diverse indolenine-fused 2H-1,4-oxathiines in moderate to high yields. A combined experimental and computational mechanistic study suggests that the reaction proceeds through addition of a S conjugate to the o-azaxylylene intermediate, followed by O-Michael addition and a sequential retro-Michael addition/pyridine extrusion pathway.

Catalytic Asymmetric Synthesis of Vicinally Bis(trifluoromethyl)-Substituted Molecules via Normal [3 + 2] Cycloaddition of N-2,2,2-Trifluoroethyl Benzothiophene Ketimines and ß-Trifluoromethyl Enones.

An organocatalytic asymmetric [3 + 2] cycloaddition of ß-trifluoromethyl enones with 3-(N-2,2,2-trifluoroethyl) benzothiophene ketimines and 2-(N-2,2,2-trifluoroethyl) benzothiophene ketimines was described for the first time. A wide spectrum of vicinally bis(trifluoromethyl)-substituted spiro pyrrolidine-benzothiophenones were obtained with excellent stereocontrol (all cases >20:1 dr and up to 99% ee). The highlight of this work is the extremely high efficiency in the construction of spirocyclic benzothiophenone derivatives possessing a vicinally bis(trifluoromethyl)-substituted pyrrolidine moiety with four contiguous stereocenters.