Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Objective:To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application.Methods:This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively.Results:All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] ( Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] ( Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] ( Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] ( Z=-2.81, P=0.005). Conclusions:A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Objective:To investigate the characteristics of gut microbiota in patients with type 2 diabetes (T2DM) complicated by nonalcoholic fatty liver disease (NAFLD).Methods:A total of 74 patients first diagnosed with T2DM at the Endocrinology Department of Peking Union Medical College Hospital from April 2021 to October 2023 were included. Among them, 28 patients had concurrent NAFLD while 46 patients did not. Additionally, 51 healthy controls were matched (HC group). Clinical laboratory parameters were collected, and 16S rRNA sequencing with fecal samples was conducted to compare the differences in gut microbiota across the groups.Results:Compared to the group with T2DM, patients with concurrent T2DM and NAFLD were younger, had higher level of insulin resistance as assessed by the homeostatic model assessment of insulin resistance, higher body mass index (BMI), and higher triglyceride levels. There was no difference in α-diversity across the three groups ( P>0.05), while there was a significant difference in β-diversity ( P=0.03). The Eubacterium coprostanoligenes, Fusicatenibacter, Parasutterella and Tyzzerella 3 were enriched in the group with concurrent T2DM and NAFLD as shown by the relative abundance, while the relative abundance of Flavonifractor was decreased in this group. Tyzzerella 3 abundance was positively correlated with triglyceride and albumin levels and negatively correlated with high-density lipoprotein cholesterol (HDL-C) levels. Conclusion:Patients with T2DM complicated by NAFLD exhibit dysbiosis in gut microbiota composition and specific genera abundance, with Flavonifractor identified as a potential protective factor for T2DM complicated by NAFLD.

The ApoE gene is a genetic risk determinant for sporadic Alzheimer′s disease (AD). The ApoEε4 allele increases the risk of developing AD relative to the common ApoEε3 allele, whereas the ApoEε2 allele decreases the risk of developing the disease. The 3 alleles encode ApoE2, ApoE3, and ApoE4 protein isoforms, respectively. ApoE4 contributes to the pathogenesis of AD by regulating β-amyloid protein, tau protein, transactive response DNA-binding protein-43, neuroinflammation, and cerebral vascular function. The pathways associated with ApoE also offer new opportunities for the treatment of AD. In addition, studies have shown that ApoE4 also plays a toxic role in other neurological disorders. This article described the biological characteristics of ApoE, as well as the impact of ApoE4 on AD and related dementias, aiming to enhance clinical doctors′ understanding of the involvement of ApoE4 in the pathogenesis of AD and related dementia.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Objective:To analyze the clinical characteristics of novel coronavirus (COVID-19) infection in liver transplant recipients.Methods:Clinical data of 130 liver transplant recipients with COVID-19 infection followed in Hebei Medical University Third Hospital from November 2022 to January 2023 were retrospectively collected, including 103 males and 27 females, aged (53.6±11.4) years. The severity of COVID-19 infection, its clinical symptoms, and negative conversion time for each recipient were analyzed and compared.Results:For the disease severity, 121 (93.1%) were mild, 5 (3.8%) were moderate, 3 (2.3%) were severe, and 1 (0.8%) was critically severe. The most common symptoms in the 126 patients with mild to moderate COVID-19 infection were successively fever, fatigue, cough and myalgia, with a negative conversion time of (10.1±4.5) (3.0-29.0)d. In those who underwent transplantation less than 12 months ( n=28), those who were taking mycophenolate mofetil ( n=53) and those who were taking methylprednisolone ( n=10), the negative conversion time was (11.6±5.1) d, (11.4±5.4) d, and (13.4±6.4) d, respectively, longer compared to those who underwent transplantation more than 12 months (9.7±4.2 d, n=98), and who were not taking mycophenolate mofetil (9.2±3.4 d, n=73) or methylprednisolone (9.8±4.2 d, n=116, all P<0.05). The negative conversion times were longer in recipients with symptoms (eg. fatigue and cough) than those in asymptomatic recipients (11.0±5.1 d vs. 9.0±3.3 d, t=2.64, P=0.009, and 11.4±5.2 d vs. 9.0±3.4 d, t=2.92, P=0.004). Conclusion:The COVID-19 infection in liver transplant recipients was mainly mild and moderate. The most common symptoms are fever, fatigue, cough and myalgia. The short time (less than 12 months) after liver transplantation, oral mycophenolate mofetil and methylprednisolone, with symptoms (fatigue and cough) could be associated with a prolonged negative conversion time.

Objective:To evaluate the effect of metformin on ultraviolet A (UVA) -induced photoaging of an immortalized human keratinocytes cell line (HaCaT), and to explore its potential mechanisms.Methods:Cell counting kit 8 (CCK8) assay was performed to evaluate the effect of metformin at different concentrations (0 - 100 mmol/L) on the viability of HaCaT cells, and 10 mmol/L metformin was selected for subsequent experiments. Cultured HaCaT cells were divided into a blank control group (conventional culture), a metformin group (treated with culture medium containing 10 mmol/L metformin), a UVA irradiation group (conventional culture for 24 hours followed by 10 J/cm 2 UVA irradiation) and a metformin + UVA group (treated with culture medium containing 10 mmol/L metformin for 24 hours followed by 10 J/cm 2 UVA irradiation) ; UVA irradiation was performed at a dose of 10 J/cm 2 once a day for 3 consecutive days. After 4-day treatment, cells were collected, the β-galactosidase assay was performed to determine the proportion of senescent cells in each group, 2′, 7′-dichlorodihydrofluorescein diacetate assay to detect levels of intracellular reactive oxygen species (ROS), and the comet assay to detect DNA damage levels. Additionally, some HaCaT cells were divided into the blank control group, metformin group, 1.25 μmol/L dorsomorphin (an adenosine monophosphate-activated protein kinase [AMPK] inhibitor) + metformin group, and 2.5 μmol/L dorsomorphin + metformin group, and cells in the latter two groups were treated with 1.25 and 2.5 μmol/L dorsomorphin respectively for 2 hours, followed by the treatment with 10 mmol/L metformin for 24 hours. Western blot analysis was performed to determine the cellular localization and phosphorylation levels of nuclear factor-erythroid 2-related factor 2 (Nrf2). By using the small-interfering RNA (siRNA) -mediated silencing method, siRNA-Nrf2 was transfected into HaCaT cells to knock down Nrf2 expression (siRNA-Nrf2 group) ; 2.5 μmol/L dorsomorphin-treated HaCaT cells or Nrf2-knockdown HaCaT cells were treated with metformin and UVA irradiation (dorsomorphin + metformin + UVA group, siRNA-Nrf2 + metformin + UVA group, respectively), and the proportions of senescent cells were further calculated in each group. Statistical analysis was carried out by using one-way analysis of variance and two-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Treatment with different concentrations of metformin for 24 hours could affect the viability of HaCaT cells to varying degrees ( F = 5 206.31, P < 0.001) ; there were no significant differences in the relative survival rates of HaCaT cells between the 10 - 20 mmol/L metformin groups and the control group (0 mmol/L metformin group, all P > 0.05), while the relative cell survival rates were significantly lower in the 25 - 100 mmol/L metformin groups than in the control group (all P < 0.05). After UVA irradiation, HaCaT cells shrank significantly and became narrow and elongated, and the intercellular spaces increased; the relative cell survival rate was significantly lower in the UVA irradiation group (76.13% ± 1.03%) than in the blank control group (100.00% ± 1.24%, LSD- t = 14.86, P < 0.001), but significantly higher in the metformin + UVA group (106.69% ± 2.45%) than in the UVA irradiation group (LSD- t = 11.55, P < 0.001). Moreover, the UVA irradiation group showed significantly increased proportions of senescent cells (45.14% ± 4.98%), intracellular ROS levels (144.61% ± 4.91%), and percentages of DNA in the tail (75.33% ± 1.77%) compared with the blank control group (23.84% ± 1.89%, 55.49% ± 1.57%, 1.88% ± 0.29%, respectively, all P < 0.001), while the metformin + UVA group showed significantly decreased proportions of senescent cells (24.26% ± 1.34%), intracellular ROS levels (58.62% ± 2.17%), percentages of DNA in the tail (15.83% ± 1.23%) compared with the UVA irradiation group (all P < 0.001). Western blot analysis showed that the Nrf2 expression in the cytoplasm was lower in the 10 mmol/L metformin group than in the blank control group, while the phosphorylated Nrf2 expression in the nuclei was higher in the 10 mmol/L metformin group than in the blank control group, suggesting that metformin could effectively induce the phosphorylation of Nrf2 and its nuclear translocation; both the pretreatment with 1.25 and 2.5 μmol/L dorsomorphin could significantly reduce the phosphorylation levels of AMPKα and Nrf2 induced by 10 mmol/L metformin. The proportions of senescent cells in the dorsomorphin + metformin + UVA group and the siRNA-Nrf2 + metformin + UVA group were 67.84% ± 2.74% and 65.94% ± 1.33%, respectively, which were significantly higher than those in the metformin + UVA group (37.76% ± 1.64%, t = 14.45, 13.34, respectively, both P < 0.001) . Conclusion:Metformin may inhibit UVA-induced photoaging of HaCaT cells by activating the AMPK/Nrf2 signaling pathway, scavenging ROS and reducing DNA damage.