A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

OBJECTIVE: To explore the relationship between the geriatric nutritional risk index (GNRI) and cognitive function. METHODS: A cross-sectional study method was conducted. People aged ≥ 60 years from the National Health and Nutrition Examination Survey (NHANES) databases from 1999 to 2002 and 2011 to 2014 were included as study subjects. The participants were divided into three groups based on their GNRI scores: a medium-high risk group (82 ≤ GNRI < 92), a low risk group (92 ≤ GNRI < 98), and a no-risk group (GNRI ≥ 98). Demographic characteristics (gender, age, race, education), chronic diseases [chronic bronchitis, emphysema, thyroid problems, coronary heart disease, angina pectoris, stroke, hypertension, diabetes mellitus, and depression score on the patient health questionnaire (PHQ-9)], lifestyle habits (history of smoking, hours of sleep), etc., were collected. Cognitive function was assessed using the consortium to establish a registry for Alzheimer's disease word learning subtest (CERAD-WL), animal fluency test (AFT), and digit symbol substitution test (DSST) for the 2011-2014 data, while only the DSST was used for the 1999-2002 data. Differences in the above information among the GNRI cohorts were compared. Factors affecting cognitive function in the population were analyzed using multifactorial Logistic regression. RESULTS: 2 653 participants from 2011 to 2014 and 2 380 participants from 1999 to 2002 were enrolled, with a total of 5 033 participants in the study. There were statistically significant differences in age, stroke, diabetes mellitus, DSST score, AFT score, CERAD score test 1 recall (Cst1), and CERAD score test 2 recall (Cst2) among the GNRI groups. Multifactorial Logistic regression analysis of data from 2011 to 2014 showed that in model 3 (DSST score, age, gender, race, marriage, education, hours of sleep, history of smoking, emphysema, thyroid problems, chronic bronchitis, coronary heart disease, angina pectoris, hypertension, diabetes mellitus, depression score on the PHQ-9, and stroke) adjusted for all covariates, GNRI was a protective factor for DSST [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.00 to 1.05, P = 0.03]; Logistic regression analyse for 1999 to 2002 and 2011 to 2014 showed a significant association even after adjustment for covariates (OR = 1.02, 95%CI was 1.00 to 1.03, P = 0.02). Subgroup Logistic regression analyses of the total population from 2011 to 2014 showed a significant association between GNRI and DSST scores (OR = 1.02, 95%CI was 1.01 to 1.03, P < 0.001), with significant associations in the age subgroups of 60 to 64 years old, across gender, non-Hispanic Whites and Blacks, by education, and by marital status associations were significant (all P < 0.05). Subgroup Logistic regression analyse of the total populations from 1999 to 2002 and 2011 to 2014 showed a significant association between the GNRI and DSST score (OR = 1.01, 95%CI was 1.01 to 1.02, P < 0.001), but did not show a significant year difference (interaction P = 0.503), and the newly found in the smoking population the association was also more significant (P < 0.01). CONCLUSION The GNRI correlates with the presence of cognitive functions related to processing speed, sustained attention, and executive function, and may be able to serve as an indicator for the assessment or prediction of related cognitive functions.
Humans ; Cross-Sectional Studies ; Aged ; Middle Aged ; Nutrition Surveys ; Cognition ; Female ; Male ; Nutritional Status ; Risk Factors ; Geriatric Assessment

Nutritional therapy is a core component of critically ill patient management,and the enteral route has become the preferred method due to its dual roles of nutrition and non-nutrition. The use of vasoactive medications makes enteral nutrition decisions more challenging for these patients. This review systematically examines the pathophysiological effects of vasoactive medications on gastrointestinal tract of critically ill patients,the current value and safety of enteral nutrition in this patient's population,summarizes the optimal strategies for implementing enteral nutrition in these patients for clinical reference.

Objective To systematically review the clinical efficacy of paroxetine plus olanzapine versus paroxetine alone among depression complicated with sleep disorder patients in China.Methods PubMed,Embase,Cochrane Library,CINAHL,SinoMed,CNKI,VIP,WanFang Data databases,SUMsearch and Google search engine were electronically searched to collect randomized controlled trials(RCTs)of paroxetine plus olanzapine versus paroxetine in the treatment of depression complicated with sleep disorder Chinese patients from inception to April 3,2023.Two researchers independently screened the literature,extracted data and evaluated the risk of bias of the included studies,and the Meta-analysis was then performed by using RevMan 5.3 software.Results A total of 70 RCTs involving 5 683 patients were included.The results of Meta-analysis showed that:(1)the total effective rate in experimental group was significantly higher than that of the control group(OR=5.98,95％CI 4.51 to 7.94,P＜0.001);(2)Pittsburgh sleep quality index scores after treatment in the first month(MD=-2.81,95％CI-3.24 to-2.38,P＜0.001),in 2 months(MD=-2.41,95％CI-3.13 to-1.70,P＜0.001),in 3 months(MD=-2.80,95％CI-3.18 to-2.42,P＜0.001)and in 6 months(MD=-1.65,95％CI-1.83 to-1.48,P＜0.001)in experimental group were significantly lower than the control group;(3)Hamilton depression scale scores after treatment in the first month(MD=-5.79,95％CI-6.63 to-4.95,P＜0.001),in 2 months(MD=-4.33,95％CI-5.45 to-3.21,P＜0.001),in 3 months(MD=-3.76,95％CI-4.17 to-3.34,P＜0.001)and in 6 months(MD=-3.38,95％CI-3.60 to-3.15,P＜0.001)in experimental group were significantly lower than the control group;(4)Hamilton anxiety scale scores in experimental group were significantly lower than the control group(MD=-3.47,95％CI-3.78 to-3.16,P＜0.001).Conclusion Current evidence shows that,compared with the paroxetine alone in the treatment of depression complicated with sleep disorder patients in China,paroxetine plus olanzapine can effectively increase patients'total effective rate of clinical treatment,improve the sleep quality and depression symptoms in 1 month,2 months,3 months and 6 months after treatment,and also reduce patients'anxiety.Due to limited quality and quantity of the included studies,more high-quality studies are required to verify above conclusions.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell ; Microbiota

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective:To compare the biomechanical parameters of Ortho-Bridge system (OBS) and locking compression plate+locking attachment plate (LCP+LAP) in the fixation of femoral periprosthetic type B1 fracture.Methods:The same periprosthetic type B1 fracture of human femur were made, including simple fracture model and comminuted fracture model, 12 in each. And the simple fracture models were randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP+LAP system fixation group, and the complex fracture models were also randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP + LAP system fixation group. Then the four groups of models were tested by axial compression and torsion tests, and the stiffness of the models under axial compression and torsion angle of the models under torsion test were collected. The axial compression failure test was carried out to collect the vertical load of the ultimate failure test. The axial stiffness, torsion angle and axial failure load of OBS and LCP+LAP fixed simple and comminuted fractures were statistically analyzed by t test. Results:For the test of fixed simple fracture, there was no significant difference ( t=0.535, P=0.522) in the axial stiffness between the OBS group (868.87±157.14 N) and the LCP+LAP group (904.53±44.76 N), whereas the results of torsion test showed that the LCP+LAP group had a higher torsion angle 7.17°±0.52° than the OBS group 5.45°±0.44° ( t=5.616, P<0.001); When fixing comminuted fractures, the OBS group had a higher axial stiffness (145.33±10.34 N) than the LCP+LAP group (84.15±8.94 N) ( t=10.961, P<0.001), but the LCP+LAP group had a higher torsion angle 7.75°±1.17° than the OBS group 5.23°±0.31° ( t=4.652, P=0.001). Ultimate failure test data showed that the failure pressure of OBS fixed group (4 967.49±132.88 N) was higher than LCP+LAP group (3 967.41±145.16 N) ( t=12.447, P<0.001). In the LCP+LAP group, there was destruction of the contact cortex at the fracture site, while in the OBS group, there was destruction of the contact cortex at the fracture site as well as fractures around the proximal fixation screw. Conclusion:OBS group has similar axial compression resistance to LCP+LAP group, but better torsion resistance than LCP+LAP group when it is used to fix B1 simple fracture around femoral prosthesis. When comminuted fracture is fixed, the axial compression resistance and torsion resistance of OBS group are better than LCP+LAP group. The stress is dispersed during OBS fixation, which can better avoid the failure of internal fixation during early functional exercise.