ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease（AD） using bioinformatics and machine learning methods， validate them at the clinical specimen level， and predict potential traditional Chinese medicine（TCM）. MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus （GEO） database， and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected， and the relative gene expression was clinically verified by real-time polymerase chain reaction（Real-time PCR）. Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained， mainly involved in pathways of tricarboxylic acid cycle， 2-oxocarboxylic acid metabolism， and carbon metabolism. Five core cuproptosis-related genes， dihydrolipoamide dehydrogenase （DLD）， glutaminase （GLS）， pyruvate dehydrogenase E1 subunit beta （PDHB）， full name nuclear factor （erythroid-derived 2）-related factor 2 （NFE2L2）， and dihydrolipoamide branched-chain transacylase E2 （DBT） were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group， minimum mental state examination （MMSE） and Montreal cognitive assessment （MoCA） were significantly decreased in the AD group （P<0.01）， Homocysteine（Hcy）， interleukin（IL）-6， C-reactive protein（CRP） ， and β amyloid protein（Aβ） indexes were significantly increased （P<0.01）， and malondialdehyde（MDA） indexes were decreased （P<0.05）. Superoxide dismutase（SOD） levels were significantly decreased （P<0.01）. The mRNA relative expressions of NFE2L2 and DBT were up-regulated （P<0.05）， and those of DLD， GLS， and PDHB were significantly down-regulated （P<0.01）. The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth， calmness， and cold， and the five flavors including bitterness， sweetness， and pungency， and it was attributed to the meridians of the liver， spleen， stomach， and kidney， with the efficacy of tonifying Qi， activating blood， eliminating phlegm， and resoling dampness. ConclusionDLD， GLS， NFE2L2， PDHB， and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes， and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.

OBJECTIVES: To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice. METHODS: With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe²⁺, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress. RESULTS: The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe²⁺, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe²⁺, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions. CONCLUSIONS GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Hepatolenticular Degeneration/drug therapy* ; Hepatocytes/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Fatty Liver/metabolism* ; Arachidonate 15-Lipoxygenase/metabolism* ; Coenzyme A Ligases/metabolism* ; Liver/metabolism* ; Male

Objective:To investigate the alteration in iodine nutritional status and influence on thyroid function in the elderly aged≥65 years following water source modification in high iodine areas.Methods:Data from Yaoji Town, Xuzhou, Jiangsu(an area with high iodine due to water sources) of the national epidemiological survey on thyroid diseases, iodine nutrition, and diabetes(TIDE study) in 31 provinces and cities in China from 2015 to 2017 were utilized. Additionally, data from the screening, monitoring, and intervention on thyroid diseases(TOPS study) in the elderly(≥65 years) in Shunhe Town, Suqian, Jiangsu(an area with iodine levels exceeding the recommended amount), and Yaoji Town, Xuzhou from May to August 2021, are included. Each subject completed a questionnaire, physical examination, laboratory tests and thyroid ultrasound examinations. A total of 2 717 subjects aged≥65 years were included, including group 1, 258 subjects in TIDE study; Group 2, 1 313 subjects in TOPS Xuzhou area; Group 3, 1 146 subjects in TOPS Suqian area.Results:The urinary iodine concentration(UIC) in group 2 was significantly lower than that in group 1 [(235.16±67.09)μg/L vs (491.58±384.93)μg/L, P<0.001], but no significant difference compared with group 3 [(235.16±67.09) μg/L vs(231.62±66.11) μg/L, P>0.05]. The serum TSH level in group 2 was significantly lower than that in group 1 [(2.92±5.14)μIU/mL vs (4.15±9.19)μIU/mL, P<0.001]. Compared with group 2 and 3, the prevalence of subclinical hypothyroidism in the elderly in group 1 was the highest(22.48% vs 10.13% and 8.12%, P<0.001). TSH levels were linearly correlated with age in both excessive iodine and more than adequate iodine nutrition areas. TSH level was gradually increased with age. Conclusion:The alteration in TSH levels among the elderly is notably linked to both aging and iodine status. The prevalence of hypothyroidism in the elderly can be significantly reduced when the iodine nutrition status of the elderly returns to normal.

The treatment of craniomaxillofacial (CMF) defects and deformities is highly challenging due to the complex anatomical structures, significant individual variations and high demands for personalized reconstruction. In recent decades, the integration of cutting-edge technologies from fields such as computer science, mechanical engineering, and material science into medicine has greatly facilitated the transformation of CMF surgery from traditional, experience-based approaches to digitalized and intelligent methods. This review thoroughly analyzes the development and application areas of digital technology in CMF surgery including virtual surgical planning and facial prediction, three-dimensional printing, computer-assisted navigation and robotic surgery, virtual and mixed reality, as well as big data and artificial intelligence technologies. The aim is to offer comprehensive and in-depth reference information for the clinical practice in digital CMF surgery.

Objective:To investigate the clinical efficacy of butylphthalide combined with hyperbaric oxygen therapy on post-stroke cognitive impairment in patients with acute ischemic stroke.Methods:A total of 90 patients with post-stroke cognitive impairment who were hospitalized within 72 hours of onset in Suining County People's Hospital from December 2019 to November 2020 were included in this study. They were randomly divided into a control group and an observation group ( n = 45/group). The control group was given conventional treatment and the observation group was given butylphthalide combined with hyperbaric oxygen therapy in addition to conventional treatment. The National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score, and Activities of Daily Living score were compared between the two groups before and after treatment. Results:Before treatment, there were no significant differences in the National Institutes of Health Stroke Scale score, Montreal Cognitive Assessment score, and Activities of Daily Living score between the two groups (all P > 0.05). At 14 days and 1 month after surgery, the National Institutes of Health Stroke Scale scores in the observation group were (4.02 ± 2.18) points and (3.21 ± 2.03) points, which were significantly lower than (5.21 ± 2.24) points and (4.62 ± 2.68) points in the control group ( t =2.55, 2.81, both P < 0.05). At 1 and 3 months after treatment, the Montreal Cognitive Assessment score in the observation group were (19.79 ± 5.67) points and (23.69 ± 2.67) points, which were significantly higher than (16.88 ± 5.12) points and (19.74 ± 2.29) points in the control group ( t = 2.56, 7.53, both P < 0.05). At 1 and 3 months after treatment, Activities of Daily Living scores in the observation group were (54.85 ± 5.69) points and (74.38 ± 4.98) points, which were significantly higher than (46.78 ± 6.24) points and (63.21 ± 5.24) points in the control group ( t = 6.41, 9.76, both P < 0.05). Conclusion:Butylphthalide combined with hyperbaric oxygen therapy for the treatment of post-stroke cognitive impairment in patients with acute ischemic stroke can alleviate neurologic deficits, and improve cognitive function and the ability of daily life.

The ketogenic diet, a non-pharmacotherapy, simulates the state of fasting to induce the liver to metabolize fatty acids into ketones as fuel source. It also possesses anti-inflammatory effects and impacts the occurrence and progression of various diseases among which is polycystic ovary syndrome(PCOS). Ketogenic diet effectively manages body weight, improves ovarian function, regulates metabolic disorder, and enhances mental health. The growing body of evidence substantiates the safety and efficacy profile.

Objective:To retrieve, evaluate, and summarize the best evidence for the prevention and management of nipple pain or injury in breastfeeding puerperae, providing evidence-based basis for clinical practice of breastfeeding.Methods:According to the "6S" evidence pyramid model, clinical decisions, guidelines, expert consensus, evidence summaries, and systematic reviews on the prevention and management of nipple pain or injury in breastfeeding puerperae were systematically searched. The search period was from database establishment to March 10, 2023. The research team members independently evaluated the quality of the included article based on the corresponding quality evaluation standards, and combined professional judgment to extract and summarize evidence for the final included article.Results:A total of 15 articles were included, including two clinical decisions, 7 guidelines, and 6 systematic reviews. Finally, 19 best pieces of evidence were summarized, including four themes, namely, assessment of nipple pain or injury, prevention of nipple pain or injury, management of nipple pain or injury, and health education.Conclusions:Obstetrical nurses and midwives should provide standardized nursing for breastfeeding puerperae based on specific clinical scenarios, reduce the incidence of nipple pain or injury in breastfeeding puerperae, and promote puerperae to adhere to breastfeeding.

ObjectiveTo explore the characteristics of eye collaterals of patients with hepatic Wilson's disease （WD） and intervention effect of Gandouling （GDL） based on digital diagnosis information on eyes， in order to provide references for the clinical efficacy of GDL in the treatment of patients with hepatic WD. MethodEighty-two patients with hepatic WD （WD group） and 68 healthy volunteers （normal control group， NC） were enrolled. Eye images of all subjects were collected by the ophthalmoscope， followed by digital extraction of eye collateral characteristics. Differences in main eye collateral characteristics between the WD group and the NC group were analyzed. Pearson correlation test was used to analyze the eye collateral characteristics， serological indexes of liver damage ［alanine aminotransferase （ALT），aspartate transaminase （AST），and albumin （ALB）］， and Child-Pugh score in patients with hepatic WD. The 82 patients with hepatic WD were divided into a treatment group （42 cases） and a control group （40 cases）. All patients were treated with sodium 2，3-dimercapto-1-propane sulfonate （DMPS）， while those in the treatment group received additional GDL Tablets. One course of treatment contained eight days， and the treatment lasted six courses. The effects of GDL intervention on the levels of ALT，AST， and ALB，as well as the eye collateral characteristics score and Child-Pugh score were evaluated. Result① Compared with the NC group，the WD group had higher scores of "Qiu" （P<0.05） and "Xuemai" （P<0.05），which are the characteristics of eye collaterals. ② The levels of ALT and AST， and Child-Pugh score in patients with hepatic WD were positively correlated with the scores of "Qiu" and "vessel"，while the ALB level was negatively correlated with the "bulge" and "Xuemai" scores. ③ Compared with the conditions before treatment，the serum ALT and AST levels，Child-Pugh score，and the "Qiu" and " Xuemai " scores of the two groups were reduced （P<0.01），and the ALB levels were increased （P<0.01）. ④ Compared with the control group after treatment，the treatment group showed improved levels of ALT and ALB and the scores of "Qiu" and "Xuemai" （P<0.05）and better Child-Pugh score （P<0.01）. There was no significant difference in AST between the two groups. ConclusionCompared with healthy people，hepatic WD patients showed higher scores of "Qiu" and "Xuemai"， indicating that patients with hepatic WD were mainly characterized by dampness and heat，and the scores of "Qiu" and "Xuemai" were positively correlated with the severity of liver damage. Meanwhile，copper-expelling therapy combined with GDL can significantly improve the liver function of WD patients and improve the clinical efficacy.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective: To explore the improvement influence of three combined exercise programs on sleep quality among college students with sleep disorders, so as to provide reference for the construction of exercise intervention programs for sleep disorder. Methods: A total of 35 college students with sleep disorders were randomly divided into AR group ( n =10), AM group ( n =8), RM group ( n =9) and CG group ( n =8). The three exercise groups were provided with exercise intervention for 8 weeks, 3 times/week , 60 min/time, and the CG group maintained previous lifestyle.Before and after the intervention,evaluation of subjective sleep quality and reduction rate of sleep disorder by PSQI, and Actigraph GT3X+ was used to monitor the changes in the objective sleep quality. Results: After the intervention,the total score of PSQI ( t =3.49, 2.31, 2.73), sleep quality score ( t =2.71, 3.00 , 5.29),sleep duration of AR group ( t =2.74), daytime dysfunction of AM group ( t =2.64) and sleep duration of RM group ( t = 2.29) significantly decreased ( P ＜0.05); The scores of sleep duration in AM group were significantly lower than those in AR group, and the scores of PSQI,sleep quality and daytime dysfunction in AM group were significantly lower than those in CG group (P<0.05). After intervention,TST ( t =-4.41, -8.37, -6.79) and SE ( t =-4.40, -5.86, -4.91) of AR group, AM group and RM group significantly increased( P <0.05), SOL ( t =4.18, 9.93), WASO ( t =2.91, 3.46) and NA ( t =4.80, 3.37) of AM group and RM group significantly decreased ( P <0.05). The changes of TST,SE and WASO in RM group were significantly higher than those in CG group, and SOL was significantly lower than those in CG group ( P <0.05). Conclusion The three kinds of combined exercise programs can improve the subjective and objective sleep quality of college students with sleep disorders, and reduce the incidence of sleep disorders; different combined exercise programs have different influence on the improvement of sleep quality of college students with sleep disorders, aerobic combined meditative movement exercise program has a prominent influence on the improvement of subjective sleep quality, and resistance combined meditative movement exercise program has a prominent influence on the improvement of objective sleep quality.