[Colchicine alleviates myocardial ischemia-reperfusion injury in mice by activating AMPK].

OBJECTIVE: To investigate the protective effect of colchicine against myocardial ischemia-reperfusion injury (I/R) and explore the underlying mechanism. METHODS: H9C2 cells exposed to hypoxia/reoxygenation (H/R) were treated with 3 nmol/L colchicine, after which the changes in cell viability were assessed using MTT assay, and AMPK phosphorylation, the expressions of NOX4, NRF2, SOD2, BAX, Bcl-2, and cleaved caspase-3 were detected with Western blotting. Male C57BL/6 mice were randomized into sham operation, I/R, I/R+colchicine, and I/R+colchicine+dorsomorphin (DSMP) groups. After the treatments, myocardial expressions of p-AMPK/AMPK, 8-OHdG, cleaved caspase-3, mitochondrial BAX (Mito-BAX), and cytoplasmic cytochrome C (Cyt-Cyto C) were examined and cardiac functions, infarct area, ATP content, and serum levels of lactic dehydrogenase (LDH) and cardiac troponin T (cTnT) levels were assessed. RESULTS: In H9C2 cells, H/R exposure significantly reduced AMPK phosphorylation and expressions of NRF2, SOD2, and Bcl-2, lowered cell viability, and up-regulated the expressions of NOX4, BAX, and cleaved caspase-3 (P < 0.05), and these changes were obviously alleviated by colchicine treatment (P < 0.05). In the mouse models, myocardial I/R injury significantly reduced myocardial AMPK phosphorylation level, ATP content, and expressions of NRF2, SOD2 and Bcl-2, caused cardiac function impairment, enhanced NOX4, Mito-BAX, Cyt-Cyto C, BAX, 8-OHdG, and cleaved caspase-3 expressions, and increased infarct area and serum LDH and cTnT levels (P < 0.05). Colchicine treatment significantly reversed the damaging effects of I/R (P < 0.05), but its protective effects was obviously antagonized by DSMP (P < 0.05). CONCLUSION: Colchicine alleviates myocardial I/R injury and protects cardiac function in mice by reducing myocardial oxidative stress and apoptosis via activating AMPK.

Theoretical Study on Ethylamine Dissociation Reactions Using VRC-VTST and SS-QRRK Methods.

Barrierless bond dissociation reactions play an important role in fuel combustion. In this work, the pressure-dependent dissociation rate constants of ethylamine (EA) are accurately determined using variable-reaction-coordinate variational transition-state theory combined with the system-specific quantum Rice-Ramsperger-Kassel method. Before the kinetics calculations, the performances of four density functional theory methods in describing the bond dissociation of EA are evaluated against the benchmark method, FIC-MRCISD(T)+Q/cc-pVTZ, and the MN15-L/cc-pVTZ method is the best choice. By comparison of the Gibbs free energies and the rate constants for the bond dissociation reactions of EA, ethanol, and propane, the influence of functional groups on the reaction kinetics is discussed. The kinetics calculations show that the dissociation rate constants of EA are sensitive to pressure at low pressures and high temperatures, and the dominant channel is the reaction that yields C2H5 and NH2 radicals. A literature combustion model of EA is updated with our calculations, and the satisfactory agreement between the model predictions and reported ignition delay times of EA suggests the reliability of our calculations.

Association of adverse and positive childhood experiences with health-related quality of life in adolescents.

OBJECTIVES: To investigate the independent impacts of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) on the health-related quality of life (HRQOL) of Chinese adolescents, and to explore the potential moderating role of PCEs in the association between ACEs and HRQOL. STUDY DESIGN: This was a cross-sectional study. METHODS: We surveyed 6982 students aged 11-20 in Guangzhou, China, from November to December 2021. Adolescents self-reported their ACEs, PCEs, and HRQOL by the Childhood Trauma Questionnaire Short Form, the Adverse Childhood Experiences-International Questionnaire, the Benevolent Childhood Experiences Scale, and the Paediatric Quality of Life Inventory Version 4.0, respectively. Multivariable linear regressions were performed to examine the associations between ACEs, PCEs, and HRQOL controlled for adolescents' age, gender, single-child status, boarding school attendance, primary caregivers, as well as parental age and occupational status. Likelihood-ratio tests were further applied to explore the moderating role of PCEs. RESULTS: In the models that considered both ACEs and PCEs, ACEs were significantly associated with lower HRQOL scores in all dimensions, summary scales, and total scale (ß = -13.88, 95% confidence interval [CI]: -14.82, -12.94 for total scale). Conversely, exposure to an above-average number of PCEs was associated with higher HRQOL scores in all measured aspects (ß = 7.20, 95%CI: 6.57, 7.84 for total scale). PCEs significantly moderated the association between ACEs and all HRQOL dimensions, summary scales, and total scale, except school functioning. CONCLUSION: ACEs and PCEs exert independent and opposite impacts on adolescents' HRQOL. PCEs could mitigate the negative impacts of ACEs. Enhancing resilience, like PCEs, may contribute to improving the HRQOL among adolescents who have exposed to ACEs.

[The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection].

Objectives: This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs). Methods: The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit). Results: All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively. Conclusions: This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

[Clinical features of peripheral neuropathy with livedo reticularis: an analysis of seven cases].

The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.

Effect of SIRT1 gene single-nucleotide polymorphisms on susceptibility to type 1 diabetes in a Han Chinese population.

AIMS: SIRT1 deficiency has been associated with diabetes, and a variant of the SIRT1 gene has been found to be involved in human autoimmune diabetes; however, it is unclear whether this genetic variation exists in Han Chinese with type 1 diabetes (T1D) and whether it contributes to development of T1D. Therefore, we aimed to explore the association of the SIRT1 gene single-nucleotide polymorphisms (SNPs) rs10997866 and rs3818292 in a Han Chinese population with T1D. METHODS: This study recruited 2653 unrelated Han Chinese individuals, of whom 1289 had T1D and 1364 were healthy controls. Allelic and genotypic distributions of SIRT1 polymorphisms (rs10997866 and rs3818292) were determined by MassARRAY. Basic characteristics, genotype and allele frequencies of selected SNPs were compared between the T1D patients and healthy controls. Further genotype-phenotype association analysis of the SNPs was performed on the T1D patients divided into three groups according to genotype. Statistical analyses included the chi-square test, Mann‒Whitney U test, Kruskal‒Wallis H test and logistic regression. RESULTS: The allelic (G vs. A) and genotypic (GA vs. AA) distributions of SIRT1 rs10997866 were significantly different in T1D patients and healthy controls (P = 0.039, P = 0.027), and rs10997866 was associated with T1D susceptibility under dominant, overdominant and additive models (P = 0.026, P = 0.030 and P = 0.027, respectively). Moreover, genotype-phenotype association analysis showed the GG genotype of rs10997866 and the GG genotype of rs3818292 to be associated with higher titers of IA-2A (P = 0.013 and P = 0.038, respectively). CONCLUSION: SIRT1 rs10997866 is significantly associated with T1D susceptibility, with the minor allele G conferring a higher risk of T1D. Moreover, SIRT1 gene rs10997866 and rs3818292 correlate with the titer of IA-2A in Han Chinese individuals with T1D.

Three-dimensional bone remodelling of glenoid fossa in patients with skeletal Class III malocclusion after bimaxillary orthognathic surgery.

This study aimed to characterize three-dimensional quantitative morphological changes of glenoid fossa in patients with skeletal Class III malocclusion treated with bimaxillary orthognathic surgery. Ninety-five eligible patients (50 male, 45 female; mean age 22.09 years) were enrolled retrospectively. Cone beam computed tomography obtained at 1 week preoperatively (T0), immediately after surgery (T1), and at ≥ 12 months postoperatively (T2) were registered based on cranial base using voxel-based registration in 3D Slicer. Glenoid fossa surface was divided spatially into four regions, and bone modelling in these regions was visualized with color maps. Our data revealed that the mean surface variations of glenoid fossa were small, with modest bone formation as a whole. No significant associations between anteroposterior or vertical mandibular displacement and overall glenoid fossa remodeling were found (P > 0.05). Moreover, bone deposition was frequently observed in the anterior-lateral region of glenoid fossa in patients with a larger mandibular movement during T0-T1 (P < 0.001). Paired bone formation in the anterior-lateral region of glenoid fossa and bone resorption in the anterior-lateral region of condylar head was frequently observed. Collectively, our results revealed that glenoid fossa underwent complex but modest bone remodeling after bimaxillary surgery in skeletal Class III patients.

Efficacy and safety of stellate ganglion block with different volumes of ropivacaine to improve sleep quality in patients with insomnia: a comparative study.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasound-guided stellate ganglion block (SGB) with different volumes of 0.375% ropivacaine on sleep quality in patients with insomnia. PATIENTS AND METHODS: A total of 80 patients who were selected to undergo SGB for the treatment of insomnia were enrolled. The patients were divided into saline control group, and low-volume (4 mL), medium-volume (6 mL), and high-volume (8 mL) ropivacaine injection groups according to the random table method. The treatment included 7 blocks with once every three days. The left and right stellate ganglions are alternately blocked. The onset and maintenance time of Horner syndrome, the degree of carotid artery dilation and blood flow velocity before and 20 minutes after the first block, the occurrence of complications such as drug crossing of the midline of the artery and hoarse throat were recorded, and the improvement of sleep disorders was evaluated with the Pittsburgh Sleep Quality Index Scale. RESULTS: Horner syndrome occurred in 100% of all volumes of ropivacaine block. The ipsilateral internal carotid artery was dilated and was accompanied by increased blood flow. The degree of dilation and increase in blood flow were not affected by the volumes of drug injection. There were no serious complications in any group, but the incidences of hoarseness and dysphagia were higher in the medium- and high-volume groups than those in the low-volume group (all p < 0.05). Compared with the low- and medium-volume groups, the high-volume group had a faster onset of action, longer maintenance time, and the highest chance of the drug crossing the artery (all p < 0.05). Compared to those before the pre-block and in the control groups, insomnia was improved in all volume groups after the block with nonsignificant intergroup differences. CONCLUSIONS: 4 mL of 0.375% ropivacaine for ultrasound-guided SGB is sufficient to improve the sleep quality of insomnia patients, whose overall risk is lower than block with 6 mL or 8 mL of ropivacaine.

[Topography-guided transepithelial corneal collagen cross-linking by sequential ultraviolet A irradiation in different diameters for progressive keratoconus in adults].

Objective: To compare the efficacy and safety of a novel customized topography-guided transepithelial corneal collagen cross-linking (TG-CXL) procedure by sequential ultraviolet A irradiation in different diameters and conventional transepithelial corneal collagen cross-linking (TE-CXL) in adult patients with progressive keratoconus. Methods: A prospective cohort study was conducted. Adult patients diagnosed with progressive keratoconus in the Affiliated Xiamen Eye Center of Xiamen University were continuously recruited and randomly assigned to receive the TG-CXL or TE-CXL procedure from March 2020 to March 2021. Patients in the TE-CXL group were irradiated in the central 9-mm zone of the cornea (total energy, 7.2 J/cm2; irradiance, 45 mW/cm2), while patients in the TG-CXL group were first irradiated with the protocol used in the TE-CXL group, and further irradiated in the central 6-mm zone (total energy, 3.6 J/cm2; irradiance, 9 mW/cm2). The subjective symptom of pain and corneal fluorescein sodium staining were scored within postoperative 3 days. Slit lamp examination, measurements of uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), corneal topography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy, corneal endothelial cell count, and non-contact tonometry were performed before surgery and at 3, 6, and 12 months after surgery. Results: A total of 66 patients were enrolled (mean age, 23.0±3.3 years old), with 33 patients (33 eyes) in each group. No statistically significant differences were found in age, gender, and maximum keratometry (Kmax) between the two groups (P>0.05). On day 1 after surgery, the average pain score of the TG-CXL group (2.21±0.45) was significantly higher than that of the TE-CXL group (1.32±0.33) (P<0.05). The pain was rapidly alleviated in both groups on days 2 and 3. On days 1 and 2, the corneal fluorescein sodium staining scores in the TG-CXL group (4.15±0.83 and 2.21±0.60, respectively) were significantly higher than those in the TE-CXL group (1.76±0.56 and 0.85±0.51, respectively, P<0.001), while there was no significant difference between the two groups at day3 (P=0.184). The UCVA and BCVA of the TG-CXL group at 3, 6, and 12 months after surgery were significantly improved when compared with the baseline. At 3, 6, and 12 months, the BCVA (LogMAR) of the TG-CXL group (0.21±0.15, 0.22±0.16, and 0.22±0.16, respectively) were significantly improved when compared with those of the TE-CXL group(0.32±0.15, 0.34±0.15, and 0.36±0.16, respectively, P<0.01). However, there was no significant difference in UCVA between groups at any time point after surgery (P>0.05). The spherical and cylindrical power values of the TG-CXL group were improved when compared with the baseline (P<0.05). However, no significant difference in spherical power values was found between the two groups at any time point after surgery (P>0.05). Meanwhile, there were significant differences in cylindrical power values between the two groups at 6 and 12 months after surgery (P<0.05). The Kmax in the TG-CXL group was improved at all of the time points after surgery when compared with the baseline (P<0.001), while no significant difference in Kmax was found at any time point after surgery in the TE-CXL group when compared with the baseline (P>0.05). At 6 and 12 months after surgery, the Kmax values in the TG-CXL group were significantly lower than the TE-CXL group (P<0.05). No significant differences were found in flat keratomety, steep keratometry, the minimal thickness of the cornea, endothelial cell density, and intraocular pressure between the two groups at any time point after surgery (P>0.05). Within one month after surgery, optical coherence tomography revealed the increased density in the anterior stroma in both groups. In most patients in the TG-CXL group, a demarcation line was visible in the central and para-central corneal stroma, representing a clear and continuous, high-signal arc-shaped linear structure, which was deeper in the central cornea than the para-central cornea. In contrast, a demarcation line, fuzzy and focally discontinuous, was visible only in a few patients in the TE-CXL group, with an almost uniform depth in the central and the para-central cornea. Confocal microscopy demonstrated an apparent mesh-like cross-linked collagen structure in the superficial and intermediate corneal stroma at all time points after surgery in the TG-CXL group, with thickening stromal collagen fibers and an increased number of interconnections. In contrast, the mesh-like structure and number of interconnections in the superficial corneal stroma were significantly reduced at 12 months after surgery in the TE-CXL group, with no cross-linking structure in the intermediate corneal stroma at any time point after surgery. No serious complications such as corneal infection, sterile corneal ulcer, and persistent epithelial defect were observed in both groups during the follow-up of 12 months. Conclusions: The TG-CXL procedure by sequential irradiation in two different diameters with ultraviolet A light was effective and safe in the management of progressive keratoconus in adults, achieving significant refractive improvement. This might be a good technical alternative for refractive corneal cross-linking surgery.

[Summary of the best evidence on exercise for the prevention and treatment of diabetic foot].

Objective: To summarize the best evidence on exercise for the prevention and treatment of diabetic foot. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve all the publicly published evidences till July 2022 on exercise for the prevention and treatment of diabetic foot, including guidelines, evidence summary, recommended practices, expert consensus, systematic review, and original research, from foreign language databases including BMJ Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Embase, PubMed, Guideline International Network, National Guideline Clearinghouse, Chinese databases including China National Knowledge Infrastructure, Wanfang Database, VIP Database, China Biology Medicine disc, China Clinical Guidelines Library, and the official websites of relevant academic organizations including National Institute for Health and Care Excellence of the United Kingdom, Registered Nurses' Association of Ontario of Canada, the International Working Group on the Diabetic Foot, International Diabetes Federation, American College of Sports Medicine, American Diabetes Association, and Chinese Diabetes Society. The literature was screened and evaluated for the quality, from which the evidences were extracted and evaluated to summarize the best evidences. Results: Nine guidelines, three expert consensuses, one evidence summary (with two systematic reviews being traced), two systematic reviews, 6 randomized controlled trials were retrieved and included, with good quality of literature. Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from the aspects of appropriate exercise prevention of diabetic foot, exercise therapy of diabetic foot, precautions for exercise, health education, and establishment of a multidisciplinary limb salvage team. Conclusions: Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from 5 aspects, providing decision-making basis for clinical guidance on exercise practice for patients with diabetic foot.

The economic burden of coronary heart disease in mainland China.

OBJECTIVES: The aim of this study was to systematically evaluate the current economic burden of coronary heart disease (CHD) in mainland China and provide a reference for the formulation of policies to reduce the economic burden of CHD. STUDY DESIGN: A systematic literature review was conducted of empirical studies on the economic burden of CHD over the past 20 years. METHODS: PubMed, Web of Science, Embase, China Knowledge Resource Integrated Database and the WANFANG database were comprehensively searched for relevant articles published between 1 January 2000 and 22 December 2021. Content analysis was used to extract the data, and Stata 17.0 software was used for analysis. The median values were used to describe trends. RESULTS: A total of 35 studies were included in this review. The annual median per-capita hospitalisation expense and the average expense per hospitalisation were $3544.40 ($891.64-$18,371.46) and $5407.34 ($1139.93-$8277.55), respectively. The median ratio on medical consumables expenses, drug expenses, medical examination expenses and treatment expenses were 41.59% (12.40%-63.73%), 26.90% (7.30%-60.00%), 9.45% (1.65%-33.40%) and 10.10% (2.36%-66.00%), respectively. The median per-capita hospitalisation expense in the eastern, central and western regions were $9374.45 ($2056.13-$18,371.46), $4751.5 ($2951.95-$8768.93) and $3251.25 ($891.64-$13,986.38), respectively. The median average expense per hospitalisation in the eastern and central regions were $6177.15 ($1679.15-$8277.55) and $1285.49 ($1239.93-$2197.36), respectively. The median average length of stay in the eastern, central and western regions were 9.3 days, 15.2 days and 16.1 days, respectively. CONCLUSIONS: The economic burden of CHD is more severe in mainland China than in developed countries, especially in terms of the direct economic burden. In terms of the types of direct medical expenses, a proportion of medical examination expenses, treatment expenses and drug expenses were lowest in the eastern region, but medical consumables expenses were the highest in this region. This study provides guidance for the formulation of policies to reduce the economic burden of CHD in mainland China.

Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study.

BACKGROUND: The 523 poly-T length polymorphism (rs10524523) in TOMM40 has been reported to influence longitudinal cognitive test performance within APOE ε3/3 carriers. The results from prior studies are inconsistent. It is also unclear whether specific APOE and TOMM40 genotypes contribute to heterogeneity in longitudinal cognitive performance during the preclinical stages of AD. OBJECTIVES: To determine the effects of these genes on longitudinal cognitive change in early preclinical stages of AD, we used the clinical trial data from the recently concluded TOMMORROW study to examine the effects of APOE and TOMM40 genotypes on neuropsychological test performance. DESIGN: A phase 3, double-blind, placebo-controlled, randomized clinical trial. SETTING: Academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. PARTICIPANTS: Cognitively normal older adults aged 65 to 83. INTERVENTION: Pioglitazone tablet. MEASUREMENTS: Participants from the TOMMORROW trial were stratified based on APOE genotype (APOE ε3/3, APOE ε3/4, APOE ε4/4). APOE ε3/3 carriers were further stratified by TOMM40'523 genotype. The final analysis dataset consists of 1,330 APOE ε3/3 carriers and 7,001 visits. Linear mixed models were used to compare the rates of decline in cognition across APOE groups and the APOE ε3/3 carriers with different TOMM40'523 genotypes. RESULTS: APOE ε3/4 and APOE ε4/4 genotypes compared with the APOE ε3/3 genotype were associated with worse performance on measures of global cognition, episodic memory, and expressive language. Further, over the four years of observation, the APOE ε3/3 carriers with the TOMM40'523-S/S genotype showed better global cognition and accelerated rates of cognitive decline on tests of global cognition, executive function, and attentional processing compared to APOE ε3/3 carriers with TOMM40'523-S/VL and VL/VL genotypes and compared to the APOE ε3/4 and APOE ε4/4 carriers. CONCLUSIONS: We suggest that both APOE and TOMM40 genotypes may independently contribute to cognitive heterogeneity in the pre-MCI stages of AD. Controlling for this genetic variability will be important in clinical trials designed to slow the rate of cognitive decline and/or prevent symptom onset in preclinical AD.

Circulating Metabolites and Dental Traits: A Mendelian Randomization Study.

It is of great importance to uncover causal biomarkers to gain insight into the pathogenesis of oral diseases and identify novel treatment targets for prevention and treatment thereof. This study aimed to systematically evaluate the causal effects of hundreds of metabolites on 10 dental traits using a 2-sample Mendelian randomization (MR) approach. Genetic variants from genome-wide association studies of 309 known metabolites were used as instrumental variables. We selected 10 dental traits, including clinical measures of dental diseases, from the Gene-Lifestyle Interactions in Dental Endpoints Consortium and self-reported oral health data from the UK Biobank. The causal relationships between metabolites and dental traits were inferred using the inverse variance-weighted approach and further controlled for horizontal pleiotropy using 5 additional MR methods. After correcting for multiple tests, 5 metabolites were identified as causal biomarkers. Genetically predicted increased levels of mannose were associated with lower risk of bleeding gums (odds ratio [OR] = 0.72; 95% confidence interval [CI], 0.61-0.85; P = 9.9 × 10-5). MR also indicated 4 metabolites on the causal pathway to dentures, with fructose (OR = 0.50; 95% CI, 0.36-0.70; P = 5.2 × 10-5) and 1-palmitoleoyl-glycerophosphocholine (OR = 0.67; 95% CI, 0.56-0.81; P = 4.8 × 10-5) as potential protective factors and glycine (OR = 1.22; 95% CI, 1.11-1.35; P = 5.6×10-5) and 1,5-anhydroglucitol (OR = 1.32; 95% CI, 1.14-1.52; P = 1.5 × 10-4) as risk factors. The causal associations were robust in various sensitivity analyses. We further observed some shared metabolites among different dental traits, implying similar biological mechanisms underlying the pathogenic processes. Finally, the pathway analysis revealed several significant metabolic pathways that may be involved in the development of dental disorders. Our study provides novel insights into the combination of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for dental disorders. It highlighted 5 metabolites and several pathways as causal candidates, warranting further investigation.

[Epidemiological characteristics of mpox epidemic in Guangzhou].

Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M(Q1,Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.

[Preliminary report on the use of total lumpectomyconical remnant gastric - esophagus side overlap anastomosis in radical resection of Siewert type II proximal gastric cancer].

Objective: There is no standard method for esophageal remnant gastric reconstruction for proximal gastrectomy. Reflux esophagitis caused by esophagogastrostomy remains a difficult surgical problem. To report the preliminary surgical results of novel esophagus-conical remnant gastric side overlap anastomosis (CGEO) , with particular emphasis on postoperative esophageal reflux. Methods: In June 2022, we developed a novel CGEO for laparoscopic proximal gastrectomy on two patients with Siewert type II esophagogastric junction adenocarcinoma. Surgical procedures for CGEO: (1) Laparoscopic proximal gastrectomy and preparation of conically shaped gastric remnant; (2) Determining anastomotic site of residual stomach and esophagus; (3) Side-to-side anastomosis of right esophageal wall to anterior of conical gastric remnant; (4) Valvuloplasty of esophageal stump. Results: Case 1 was a 71-year-old man with an operation time of 305 minutes and was successfully discharged from the hospital on the 9th day after surgery, and the postoperative pathology was T3N0M0. Case 2 was an 82-year-old man with an operation time of 325 minutes. He was discharged on the 10th day after surgery. In both cases, only mild esophageal mucosal changes were seen in gastroscopy, there were no obvious symptoms of esophageal reflux. There was also no significant weight change at half a year after operation. Conclusion: CGEO is moderately safe in radical surgery for proximal gastric cancer, and may have a preventive effect on the occurrence of postoperative esophageal reflux, but long-term results need to be confirmed by further studies with follow-up.

[Short-term outcome of patients after transcatheter aortic valve replacement receiving different anticoagulants].

Objective: To compare the safety and efficacy of different anticoagulants in patients with indications for anticoagulation after transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Patients who underwent TAVR from April 2016 to February 2022 in Guangdong Provincial People's Hospital and had indications for anticoagulation were included and divided into two groups according to the type of anticoagulants, i.e. non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin, and patients were followed up for 30 days. The primary endpoint was the combination of death, stroke, myocardial infarction, valve thrombosis, intracardiac thrombosis and major bleeding. The incidence of endpoints was compared between two groups, and multivariate logistic regression analysis was applied to adjust the bias of potential confounders. Results: A total of 80 patients were included. Mean age was (74.4±7.1) years, 43 (53.8%) were male. Forty-nine (61.3%) patients used NOAC, 31 used warfarin, and major indication for anticoagulants was atrial fibrillation (76/80, 95.0%). The adjusted risks of the primary endpoint (OR=0.23, 95%CI 0.06-0.94, P=0.040) of NOAC were lower than that of warfarin, mainly driven by a lower risk of major bleeding (OR=0.19, 95%CI 0.04-0.92, P=0.039). Conclusions: The short-term outcome of NOAC is better than that of warfarin in patients with indications for anticoagulation after TAVR. Randomized controlled trials of large sample size with long-term follow-up are needed to further testify this finding.

[Qualitative and quantitative PET/MRI in the evaluation of axillary lymph node metastasis in patients with breast cancer].

Objective: To investigate the value of qualitative and quantitative PET/MRI in the evaluation of axillary lymph node metastasis in patients with breast cancer. Methods: A total of 33 patients with breast cancer underwent preoperative PET/MRI examinations in Jingling Hospital from February to August in 2022 were retrospectively collected. All these patients were female, aged from 34 to 73 (51.4±11.3) years. Histopathological results and follow-up data were deemed as the referent standard, and the images were independently evaluated by two experienced breast imaging radiologists. The qualitative PET/MRI evaluation procedures were designed to evaluated the MRI alone to classify the axillary lymph nodes firstly, and then, the axillary lymph nodes status was reclassified by combining MRI and PET images. The net reclassification improvement index (NRI) was calculated using the R Programming Language (RStudio). The quantitative PET/MRI evaluation of the maximum standard uptake value (SUVmax) of axillary lymph nodes were measured by two radiologists, respectively, and the average value was compared with the referent standard to conduct a receiver operating characteristic (ROC) curve to select the optimal cutoff value of SUVmax. Based on the cutoff value and MRI classification results, axillary lymph nodes status was divided into quantitative PET/MRI positive or negative. The sensitivity, specificity and accuracy of MRI and quantitative PET/MRI in evaluating axillary lymph node metastasis were compared, and the area under the ROC curve (AUC) was compared. Results: There was no significant difference in sensitivity, specificity and accuracy between MRI and quantitative PET/MRI in evaluating lymph node metastasis of breast cancer (81.82% vs 95.46%; 81.82% vs 100%; 81.82% vs 96.97%) (all P>0.05). The AUC had a statistically significant difference [0.82 (0.65 to 0.93) vs 0.98 (0.85 to 1.00), P=0.026)]. According to the referent standard, in the 11 cases without ipsilateral axillary lymph node metastasis, the SUVmax was 0.83±0.18, while in the 22 cases with ipsilateral axillary lymph node metastasis, the SUVmax was [4.36 (1.77, 5.85)]. Compared with MRI alone, the NRI of qualitative PET/MRI in evaluating lymph node metastasis was 36.36% (P=0.021). Conclusion: Compared with MRI alone, quantitative PET/MRI has a higher AUC for evaluating axillary lymph node metastasis in patients with breast cancer, and qualitative PET/MRI had a better reclassification power in the evaluation of axillary lymph node metastasis.