Polygonum multiflorum （PM）， a commonly used Chinese herbal medicine in clinical practice， has been associated with frequent reports of liver injury in recent years， and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury （DILI） and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways， and it leads to the death of hepatocytes by destroying mitochondrial function， exacerbating bile acid accumulation， and inducing immune response， oxidative stress， and endoplasmic reticulum stress， thereby inducing the development and progression of DILI through multiple targets， pathways， and levels.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl₄-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl₄ olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl₄ induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

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.

Objective To explore the influence of impulsivity on digital addiction tendencies in patients with Wilson disease(WD)and its related factors.Methods A total of 66 patients with WD were included in the study which were divided into neurological WD group(42 cases)and hepatic WD group(24 cases)according to clinical manifestations.Sixty-six WD patients were included as the study subjects,including 24 cases of hepatic WD and 42 cases of neurological WD.The Chinese version of the Barratt impulsiveness scale(BIS-11-C)was used to assess patients'impulsiveness.Mobile phone addiction index(MPAI)evaluates the degree of dependence on mobile phone use.Cranial MRI was used to examine the location and cumulative frequency of the diseased brain region.Results Among the 66 WD patients,45 cases(68.2% )had the tendency of digital addiction,including 35 cases(53.0% )in the neurological WD group and 10 cases(15.2% )in the hepatic WD group.There was a statistically significant difference in the proportion of the two types of WD patients(P=0.001).The scores of BIS-11-C and MPAI scales in neurological WD group were higher than those in hepatic WD group(P<0.05).The out-of-control score in the MPAI scale is positively correlated with the attention impulsivity score(r=0.499,P=0.001),motor impulsivity score(r=0.553,P=0.001),unplanned impulsivity score(r=0.535,P=0.001),and impulse control score(r=0.653,P=0.001)in the BIS-11-C scale.Linear regression analysis showed a correlation between attention impulsivity score and frontal lobe lesions(B=-1.634,P=0.018).There was a correlation between loss of control score and frontal lobe lesions(B=-3.609,P=0.023).The withdrawal score was associated with the thalamus lesions(B=-5.047,P=0.007)and frontal lobe lesions(B=-2.204,P=0.024).Avoidance score was associated with parietal lobe lesions(B=-1.867,P=0.032).The low efficacy score was associated with the putamen lesions(B=-1.789,P=0.016)and frontal lobe lesions(B=-1.592,P=0.044).Conclusion Neurological WD patients have higher tendency of digital addiction than hepatic WD patients and the tendency of digital addiction is related to impulsivity.The digital addiction tendency of WD patients may be related to impulse control disorders caused by lesions in multiple brain regions such as the putamen,thalamus,and frontal lobe.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Objective:To analyze the clinical characteristics of elderly-onset gouty arthritis and risk factors of tophi.Methods:A total of 1 239 gout patients were retrospective selected in the outpatient department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from 2016 to 2022. According to age of onset, they were divided into the young and middle-aged group(aged<60) consisted of 826 cases, and the elderly group(aged≥60) consisted of 413 cases. Compare the clinical characteristics of elderly with Young and Middle-aged patients.Results:The systolic blood pressure, fasting blood glucose, creatinine, regular exercise, comorbidities, and tophi in the elderly group was higher than that in the middle-aged and young group. The proportion of diastolic blood pressure, serum triglycerides, eGFR, serum uric acid, alcohol consumption rate, and family history of gout was lower than that of young and middle-aged group( P<0.05); In the elderly-onset group, the initial site of arthritis was commonly observed in the first metatarsophalangeal joint. The proportion of the first attack with the upper limb joint was higher in old age group than in young and middle age group( P<0.05). Renal underexcretion type was the main subtype in the elderly group, and the proportion of overproduction type was higher than that of the young and middle-aged group( P<0.05). The logistic regression analysis showed that age, urea nitrogen, disease duration≥10 years and family history of gout were risk factors for tophi in elderly patients( P<0.05). Conclusion:The elderly-onset gout has unique clinical characteristics, characterized by a higher prevalence of tophi, a higher rate of complications. An initial site of arthritis commonly observed in the first metatarsophalangeal joint and the predominant type of uric acid excretion is renal excretion impairment. Early diagnosis and treatment, control of blood uric acid levels, smoking cessation and alcohol, regular exercise should be applied to prevent or delay the formation of tophi.

Objective:To analyze the influencing factors of gout patients and explore whether there is an interaction between serum uric acid and diastolic blood pressure affecting the onset of tophi.Methods:A total of 4 798 gout patients were retrospective selected in the outpatient Department of the Gout Clinical Medical Center of the Affiliated Hospital of Qingdao University from September 2016 to May 2020. It was divided into tophi group and non-tophi group to compare the differences in indicators. A logistic regression model was used to analyze the influencing factors of tophi, and an interaction model was constructed to analyze the interactions.Results:Multivariate logistic regression analysis showed significant associations between age, diastolic blood pressure, alcohol consumption history, gout family history, blood uric acid, urea nitrogen, and creatinine clearance and tophi formation. The results of blood uric acid-related interaction analysis showed a significant interaction between blood uric acid and diastolic blood pressure( Pinteraction=0.014), and the risk of developing tophi in low diastolic blood pressure and high diastolic blood pressure group increased by 34.4%( OR=1.344, 95% CI 1.105-1.635, P=0.003) and 95.4%( OR=1.954, 95% CI 1.558-2.450, P<0.001) in the high blood uric acid group compared with the low blood uric acid group. The results of diastolic blood pressure and blood uric acid subgroup analysis showed that there was no statistical difference in the risk of developing tophi in people with low uric acid levels( P=0.238), but in people with high uric acid levels, the risk of developing tophi was 67%( OR=1.670, 95% CI 1.379-2.022, P<0.001) higher than that in the low uric acid group. Conclusion:Age, diastolic blood pressure, combined alcohol consumption history and gout family history, blood uric acid, renal function are related to the occurrence of tophi. High uric acid and high diastolic blood pressure have interaction on the occurrence of tophi. Attention and proactive intervention shall be applied to this group of patients.

ObjectiveTo assess the specificity of P50 auditory-evoked potential in schizophrenic patients with violent and aggressive behaviors， so as to provide objective biological markers for predicting violent behaviors of schizophrenic patients. MethodsA total of135 schizophrenic patients who met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） were divided into aggressive group （n=70） and non-aggressive group （n=65） according to the assessment results of the Modified Overt Aggression Scale （MOAS）， meantime， another 60 healthy individuals matched for age and gender were set as healthy group. Then the P50 auditory-evoked potentials of all selected individuals were measured using EP/EMG system （MEB-9200， Nihon Kohden， Japan）. ResultsAmp S2 of the aggressive group was significantly higher than those of the non-aggressive group and healthy control group， with statistical differences ［（9.86±6.04）μV vs. （7.06±3.88）μV， P=0.004； （9.86±6.04）μV vs. （7.82±3.87）μV， P=0.031］. The proportion of S2/S1 ratio ≥0.5 was 72.88%， 43.86% and 30.00% in aggressive group， non-aggressive group and healthy group， which was the highest in aggressive group， with statistical differences （P<0.01）. The amplitude difference of P50 （S1-S2） of the aggressive group was lower than those of the non-aggressive group and the healthy control group， the differences were of statistical significance ［（4.35±9.39）μV vs.（9.89±8.48）μV， P=0.001； （4.35±9.39）μV vs.（13.42±9.81）μV， P<0.01］. ConclusionThe violent and aggressive behaviors in schizophrenic patients may be related to the sensory gating deficit.