Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To explore the mediating role of intolerance of uncertainty(IU)and moderating role of the negative emotion differentiation in the influence of perceived stress on anxiety among college students from a cognitive perspective.Methods A total of 271 participants were surveyed using the perceived stress scale,intolerance of uncertainty scale,depression anxiety and stress scale(Chinese version),and the test on negative emotional differentiation.SPSS 22.0 was used to perform descriptive statistics and correlation analyses and to test the moderated mediation model.Results Perceived stress affected anxiety and IU played a mediating role-perceived stress could affect anxiety through influencing IU.At the same time,the influence of IU on anxiety could be adjusted through the negative emotion differentiation.The higher the degree of negative emotion differentiation,the lower the degree of anxiety increase(β=0.17,t=5.70,P＜0.01).Conclusion It may be effective to develop training programs to reduce anxiety by regulating perceived stress,increasing acceptance of uncertainty,and improving the negative emotion differentiation,which can help individuals reduce anxiety by perceiving and adjusting anxiety-related emotional or cognitive factors in a timely manner.

Objective To analyze the differences in bone serum protein between patients with osteoporosis accompanied by obstructive sleep apnea syndrome(OSAS)and those with osteoporosis only using proteomics.Methods A total of 80 osteoporosis patients who attended our hospital between June 2022 and June 2024 were enrolled.Based on their polysomnography results,the participants were divided into an OSAS and osteoporosis comorbidity(OSAS-osteoporosis)group(n=42)and an osteoporosis only group(n=38).Propensity score matching was applied to incorporate covariates in logistic regression so that the individual characteristics of the two groups of patients were generally balanced.Following the matching procedure,a final cohort of 20 matched pairs was obtained and subsequently utilized for further analysis.The mass spectrum was obtained using laser desorption ionization mass spectrometry.Principal component analysis(PCA)was performed to assess differences in metabolic patterns between groups.Partial least squares discriminant analysis(PLS-DA)and orthogonal PLS-DA(OPLS-DA)were employed for further data analysis.Variable importance in projection(VIP)scores of each substance were calculated with OPLS-DA to screen the metabolites showing inter-group differences.Heatmaps were generated to visualize metabolic profile differences between the OSAS-osteoporosis group and the osteoporosis group.Enrichment pathway analysis was conducted on the differential identified metabolites.Results After propensity score matching,individual characteristics between the groups were well balanced.Mass spectrometry revealed significant differences between the OSAS-osteoporosis and osteoporosis groups.In the PCA score plot,the separation trend of the two groups was not significant.The PLS-DA score plot showed a discernible separation trend,with R2 and Q2 lower than those of the corresponding results of the real model,confirming the reliability of the model.OPLS-DA showed that the total R2X of the model was 0.635,R2Y was 0.879,and O2Y was 0.728,showing obvious separation trends between the two groups.A total of 16 differential metabolites were identified,including stearyl-oleyl-glycerol phosphate choline,phosphate choline,L-histidine,erucamide,2'-deoxyuridine,1-palmitoyl glycerol,thymine,tyramine,L-pyroglutamic acid,L-glutamic acid,myristate,glycerol-3-phosphate,caprylic acid,pregnenolone,L-arginine,D-4-hydroxyphenylglycine,and isobutyric acid.Heatmaps showed significant differences in metabolic profiles between the OSAS-osteoporosis group and the osteoporosis group.Pathway enrichment analysis showed that 27 metabolic pathways were involved.27 metabolic pathways.Under the conditions of P<0.05 and pathway impact>0.2,the three most significant metabolic pathways identified included mainly alanine,aspartate,and glutamate metabolism,arginine biosynthesis,and histidine metabolism.Conclusion Significant differences were observed in the metabolic profiles between patients with both OSAS and osteoporosis and those with osteoporosis alone.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To observe the effects of linalool on central and alleviating peripheral nervous system through transient receptor potential vanilloid 1 (TRPV1) pathway and its role in alleviating visceral hypersensitivity in irritable bowel syndrome (IBS).Methods:Thirty-six female newborn Sprague-Dawley (SD) rat pups in specific pothogen free was selected, among which 30 rats were used for behavioral experiments and 6 rats for electrophysiological experiment. In behavioral experiments, 30 newborn SD rats were randomly divided into normal control group (0.2 mL 0.9% sodium chloride solution was injected into the colorectal), neonatal colonic inflammation (NCI) group (0.2 mL 0.5% acetic acid was injected into the colorectal), linalool 20, 50 and 100 mg/kg groups (after NCI model successfully established, the rat were gavaged with linalool 20, 50 or 100 mg/kg at 5 weeks old). At 6 weeks old, abdominal withdrawal reflex (AWR) and pressure value of pain threshold (inflation pressure value at AWR score of 3) was observed by colorectal distention test. One hour after behavioral experiments, the expression of TRPV1 at protein level in colonic mucosa and spinal cord of each group was detected by Western blotting and immunohistochemistry. In electrophysiological experiment, female SD rats aged 6 to 7 weeks were selected to make in vitro transverse sections of the spinal cord. Five to eight neurons were randomly selected from each rat for whole-cell patch-clamp recording. The effects of linalool, tetrodotoxin and anti capsaicinand on the spontaneous excitatory postsynaptic current (sEPSC) of substantiagelatinosa neurons was recorded. Independent sample t test and paired t test were used for statistical analysis. Results:The AWR score of rats in NCI group was higher than those in normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group at 40 mmHg (1 mmHg=0.133 kPa) pressure (2.5±0.2 vs. 1.0±0.3, 1.5±0.3, 1.5±0.2, and 1.5±0.2, respectively), at 60 mmHg pressure the AWR score was higher than those in normal control group, linalool 50 mg/kg group and linalool 100 mg/kg group (3.8±0.2 vs. 2.3±0.4, 2.3±0.5, and 2.0±0.3, respectively), and the differences were statistically significant ( t=4.39, 2.45, 3.16, 3.16, 3.31, 2.88 and 5.97; P=0.001, 0.034, 0.010, 0.010, 0.008, 0.028, and<0.001). The pain threshold of rats in NCI group was lower than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group ((35.8±2.0) mmHg vs. (55.8±1.5), (49.2±2.4), (53.3±2.1), and (55.0±1.8) mmHg, respectively), and the differences were statistically significant ( t=-7.91, -4.28, -6.01, and -7.06; P<0.001, =0.002, <0.001, and <0.001). The results of Western blotting showed that the relative expression of TRPV1 at protein level in colorectal tissues of rats in NCI group was higher than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group (0.86±0.03 vs. 0.32±0.03, 0.68±0.01, 0.45±0.03, and 0.56±0.02, respectively), and the relative expression of TRPV1 at protein level in spinal dorsal horn was higher than those of normal control group, linalool 20 mg/kg group, linalool 50 mg/kg group and linalool 100 mg/kg group (0.91±0.02 vs. 0.34±0.03, 0.72±0.03, 0.51±0.06, and 0.63±0.05), and the differences were statistically significant ( t=12.44, 5.14, 9.68, 7.69, 19.14, 5.13, 6.72, and 5.60; P<0.001, <0.001, <0.001, <0.001, <0.001, <0.001, =0.001, and <0.001). There were no statistically significant differences in the frequency and the outward current of sEPSC in neurons of same glial region among rats with 2 mmol/L linalool gavaged for 4 minutes, 0.5 μmol/L tetrodotoxin and 2 mmol/L linalool gavaged for 4 minutes ( n=5, (23.84±4.81) Hz vs. (20.54±5.71) Hz, (7.60±0.35) pA vs. (7.62±0.75) pA, both P>0.05). The frequency of sEPSC administered with 2 mmol/L linalool gavaged for 4 minutes was higher than that of neurons in the same glial area administered with 10 μmol/L capsazepine and 2 mmol/L linalool gavaged for 4 minutes ( n=5, (20.17±2.55) Hz vs.(14.09±2.98) Hz), and the difference was statistically significant ( t=3.58, P=0.021); however there was no statistically significant difference in the outward current ((7.42±0.78) pA vs. (7.03±1.32) pA, P>0.05). Conclusion:Linalool can relieve visceral hypersensitivity in IBS partially through TRPV1 pathway, which may be related to the hyperpolarization of the membrane potential of neurons in glial region.

Objective:To investigate the efficacy of free superficial circumflex iliac artery perforator flap (SCIAPF) in reconstruction of the donor site of hallux nail flap.Methods:From December 2015 to December 2022, Section Ⅲ of Department of Hand Surgery of Hangzhou Plastic Surgery Hospital conducted thumb reconstruction surgery with free hallax nail flaps for 12 patients with traumatic defects of thumbs. Six patients had degloving injuries of thumb with intact bone scaffold and extensor-flexor tendon. Among the other 6 patients with thumb defects, 3 had grade I defect, 2 had grade II defect and 1 had grade Ⅲ defect, according to Gu Yudong's classification. Free SCIAPFs were used to reconstruct the donor sites of hallux nail flaps. Sizes of the flaps were 3.0 cm× 6.5 cm-9.0 cm ×7.0 cm. All donor sites in the abdomen were directly sutured. After surgery, functional evaluations of the reconstructed thumb were conducted through follow-ups at outpatient clinics and(or) by WeChat interviews, according to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, and the functional evaluation of donor feet was conducted according to the Maryland foot function evaluation standard.Results:Successful survival of the 9 cases of flap in the donor site of hallux nail flap. One patient had venous occlusion of flap and survived after timely surgical exploration. One flap had partial necrosis at the tip of flap, and the wound was eliminated with local transfer of a flap. One patient had necrosis over most of the flap with the base of the flap survived, and the wound was repaired by a stage-II skin grafting. The donor sites at groin healed in stage-I in all of 11 patients with a linear scar. One patient who had haematoma at the donor site was cured by removal of the haematoma and a re-suture. All the patients received a 3 to 24 months of postoperative follow-up. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 10 patients were in excellent and 2 in good. All of the great toes remained with original length and recovered normal flexion and extension. No patient suffered pain while walking and running. According to the Maryland foot function evaluation standard, 10 patients were in excellent and 2 in good. All SCIAPFs were satisfactory in colour and texture. Five patients had bloated flaps and underwent Hacks in the stage-Ⅱ.Conclusion:Application of a free SCIAPF in reconstruction of the donor site for hallux nail flap can effectively preserve the appearance and function of the donor site. Meanwhile, the scar in the donor site of groin is concealed with little damage, therefore the groin meets the requirements as a donor site of a flap.